radial-mobility-cytotoxic-function-retroviral-replicating-vector

Radial Mobility and Cytotoxic Function of Retroviral Replicating Vector Transduced, Non-adherent Alloresponsive T Lymphocytes

We report a novel adaptation of the Radial Monolayer Cell Migration assay, first reported to measure the radial migration of adherent tumor cells on ...

UCLA David Geffen School of Medicine

&#x9885;&#x5185;&#x611F;&#x67D3;&#x7684;&#x5C0F;&#x9F20;&#x5C0F;&#x9F20;&#x809D;&#x708E;&#x75C5;&#x6BD2;&#xFF0C;&#x51E0;&#x5BB6;&#x4EBA;&#xFF0C;&#x53EF;&#x590D;&#x7528;&#x5BFC;&#x81F4;&#x6025;&#x6027;&#x4E0E;&#x6162;&#x6027;&#x8131;&#x9AD3;&#x9798;&#x75BE;&#x75C5;&#x8FDB;&#x5C55;&#x7684;&#x6027;&#x8111;&#x810A;&#x9AD3;&#x708E;&#x3002;&#x968F;&#x540E;&#x795E;&#x7ECF;&#x75C5;&#x7406;&#x5B66;&#x6162;&#x6027;&#x671F;&#x7684;&#x75BE;&#x75C5;&#x662F;&#x4E3B;&#x8981;&#x514D;&#x75AB;&#x4ECB;&#x5BFC;&#x548C;&#x7C7B;&#x4F3C;&#x4E8E;&#x4EBA;&#x7C7B;&#x7684;&#x8131;&#x9AD3;&#x9798;&#x75BE;&#x75C5;&#x591A;&#x53D1;&#x6027;&#x786C;&#x5316;&#x75C7;&#x3002;&#x8D8B;&#x5316;&#x56E0;&#x5B50;&#x5728;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x5185;&#x7684;&#x5206;&#x6CCC;&#x4FE1;&#x53F7;&#x6E17;&#x900F;&#x7684;&#x767D;&#x7EC6;&#x80DE;&#xFF0C;&#x8FD9;&#x4F1A;&#x5BFC;&#x81F4;&#x6BC1;&#x706D;&#x6027;&#x7684;&#x767D;&#x8D28;&#x548C;&#x795E;&#x7ECF;&#x529F;&#x80FD;&#x7F3A;&#x635F;&#x3002;CC &#x8D8B;&#x5316;&#x56E0;&#x5B50;&#x914D;&#x4F53; (CCL) 5 &#x5728;&#x7ECF;&#x5386;&#x8131;&#x9AD3;&#x9798;&#xFF0C;&#x6697;&#x793A;&#x6B64;&#x8D8B;&#x5316;&#x56E0;&#x5B50;&#x75C5;&#x53D1;&#x75C5;&#x673A;&#x5236;&#x7684;&#x53C2;&#x4E0E;&#xFF0C;&#x5438;&#x5F15;&#x708E;&#x75C7;&#x7EC6;&#x80DE;&#x8FDB;&#x5165;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x767D;&#x8D28;&#x672C;&#x5730;&#x5316;&#x3002;&#x5728;&#x8FD9;&#x9879;&#x7814;&#x7A76;&#xFF0C;&#x6211;&#x4EEC;&#x7BA1;&#x7406;&#x4EBA;&#x4E0E;&#x751F;&#x7269;&#x5708;&#x65B9;&#x6848;&#x9488;&#x5BF9; CCL5 &#x5BF9;&#x5C0F;&#x9F20;&#x4E0E;&#x65E2;&#x5B9A;&#x7684;&#x9F20;&#x6807;&#x809D;&#x708E;&#x75C5;&#x6BD2;&#x8BF1;&#x5BFC;&#x8131;&#x9AD3;&#x9798;&#x548C;&#x53D7;&#x635F;&#x7684;&#x8FD0;&#x52A8;&#x6280;&#x80FD;&#x3002;&#x6297; CCL5 &#x6CBB;&#x7597;&#x51CF;&#x5C11;&#x7684; T &#x7EC6;&#x80DE;&#x5728;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x5185;&#x7684;&#x79EF;&#x7D2F;&#x90E8;&#x5206;&#xFF0C;&#x57FA;&#x4E8E;&#x75C5;&#x6BD2;&#x6027;&#x94F6;&#x7279;&#x5F02;&#x6027;&#xFF0C;&#x6307;&#x793A;&#x7684;&#x80FD;&#x529B;&#x5DEE;&#x5F02;&#x76EE;&#x6807;&#x9009;&#x62E9; T &#x7EC6;&#x80DE;&#x7FA4;&#x4F53;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x653F;&#x5E9C;&#x5F53;&#x5C40;&#x7684;&#x53CD; CCL5 &#x6539;&#x5584;&#x795E;&#x7ECF;&#x529F;&#x80FD;&#x548C;&#x663E;&#x8457; (p &lt; &#x6216; = 0.005) &#x51CF;&#x5C11;&#x8131;&#x9AD3;&#x9798;&#x548C;&#x5DE8;&#x566C;&#x7EC6;&#x80DE;&#x7684;&#x79EF;&#x7D2F;&#xFF0C;&#x5728;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x5185;&#x7684;&#x4E25;&#x91CD;&#x7A0B;&#x5EA6;&#x3002;&#x8FD9;&#x4E9B;&#x7814;&#x7A76;&#x7ED3;&#x679C;&#x663E;&#x793A;&#x53EF;&#x4EE5;&#x4F7F;&#x7528;&#x5728;&#x8131;&#x9AD3;&#x9798;&#x7684;&#x75C5;&#x6BD2;&#x6A21;&#x578B;&#x4E2D;&#x9488;&#x5BF9; CCL5 &#x4E2D;&#x548C;&#x4EBA;&#x4E0E;&#x751F;&#x7269;&#x5708;&#x65B9;&#x6848;&#x51CF;&#x5C11;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x75BE;&#x75C5;&#x7684;&#x4E25;&#x91CD;&#x7A0B;&#x5EA6;&#x3002;

&#x6297;&#x4F53;&#x9488;&#x5BF9; CC &#x8D8B;&#x5316;&#x56E0;&#x5B50;&#x914D;&#x4F53; 5 &#x5BFC;&#x81F4;&#x767D;&#x7EC6;&#x80DE;&#x51CF;&#x5C11;&#x7684;&#x6E17;&#x900F;&#x5230;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#xFF0C;&#x5E76;&#x51CF;&#x5C11;&#x795E;&#x7ECF;&#x75BE;&#x75C5;&#x7684;&#x75C5;&#x6BD2;&#x6A21;&#x578B;&#x7684;&#x591A;&#x53D1;&#x6027;&#x786C;&#x5316;&#x75C7;&#x3002;

Intracerebral infection of mice with mouse hepatitis virus, a member of the Coronaviridae family, reproducibly results in an acute encephalomyelitis that progresses to a chronic demyelinating disease. The ensuing neuropathology during the chronic stage of disease is primarily immune mediated and similar to that of the human demyelinating disease multiple sclerosis. Secretion of chemokines within the CNS signals the infiltration of leukocytes, which results in destruction of white matter and neurological impairment. The CC chemokine ligand (CCL)5 is localized in white matter tracts undergoing demyelination, suggesting that this chemokine participates in the pathogenesis of disease by attracting inflammatory cells into the CNS. In this study, we administer a mAb directed against CCL5 to mice with established mouse hepatitis virus-induced demyelination and impaired motor skills. Anti-CCL5 treatment decreased T cell accumulation within the CNS based, in part, on viral Ag specificity, indicating the ability to differentially target select populations of T cells. In addition, administration of anti-CCL5 improved neurological function and significantly (p < or = 0.005) reduced the severity of demyelination and macrophage accumulation within the CNS. These results demonstrate that the severity of CNS disease can be reduced through the use of a neutralizing mAb directed against CCL5 in a viral model of demyelination.

Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple sclerosis.

L&#x26;#39;infection des souris par voie intrac&#xE9;r&#xE9;brale avec la souris virus de l&#x26;#39;h&#xE9;patite, un membre de la famille des Coronaviridae, reproductible des r&#xE9;sultats dans une enc&#xE9;phalomy&#xE9;lite aigu&#xEB; qui &#xE9;volue &#xE0; une maladie d&#xE9;my&#xE9;linisante chronique. La neuropathologie qui a suivi pendant la phase chronique de la maladie &#xE0; m&#xE9;diation immunitaire est essentiellement et similaire &#xE0; celle de la scl&#xE9;rose multiple maladie d&#xE9;my&#xE9;linisante humaine. La s&#xE9;cr&#xE9;tion de chimiokines dans les CNS signale l&#x26;#39;infiltration des leucocytes, ce qui entra&#xEE;ne la destruction de la substance blanche et des troubles neurologiques. Le ligand des chimiokines CC (CCL) 5 est localis&#xE9;e dans la substance blanche en cours de d&#xE9;my&#xE9;linisation, ce qui sugg&#xE8;re que cette chimiokine participe &#xE0; la pathog&#xE9;nie de la maladie en attirant des cellules inflammatoires dans le SNC. Dans cette &#xE9;tude, nous administrons un mAb dirig&#xE9;s contre CCL5 &#xE0; des souris atteintes de l&#x26;#39;h&#xE9;patite de la souris mis en place induite par le virus d&#xE9;my&#xE9;linisation et de la motricit&#xE9; r&#xE9;duite. Anti-CCL5 traitement diminution de l&#x26;#39;accumulation des cellules T dans le SNC base, en partie, sur Ag sp&#xE9;cificit&#xE9; virale, indiquant la capacit&#xE9; de cibler de mani&#xE8;re diff&#xE9;rentielle les populations de s&#xE9;lection de cellules T. En outre, l&#x26;#39;administration d&#x26;#39;anti-CCL5 la fonction neurologique am&#xE9;lior&#xE9;e et de fa&#xE7;on significative (p &#x26;lt;ou = 0,005) a r&#xE9;duit la s&#xE9;v&#xE9;rit&#xE9; de la d&#xE9;my&#xE9;linisation et l&#x26;#39;accumulation de macrophages dans le SNC. Ces r&#xE9;sultats d&#xE9;montrent que la s&#xE9;v&#xE9;rit&#xE9; de la maladie du SNC peuvent &#xEA;tre r&#xE9;duits par l&#x26;#39;utilisation d&#x26;#39;un neutralisant mAb dirig&#xE9;s contre CCL5 dans un mod&#xE8;le de d&#xE9;my&#xE9;linisation virale.

Anticorps ciblant du ligand CC Chemokine 5 R&#xE9;sultats dans l&#x26;#39;infiltration leucocytaire diminu&#xE9;e dans le syst&#xE8;me nerveux central et r&#xE9;duit maladie neurologique dans un mod&#xE8;le viral de la scl&#xE9;rose en plaques

Antik&#xF6;rper, der auf der CC-Chemokin-Liganden 5 f&#xFC;hrt zu einer verminderten Leukozyten-Infiltration in das zentrale Nervensystem und weniger neurologische Erkrankung in einem viralen Modell der Multiplen Sklerose.

Infezione intracerebrale di topi con il virus dell&#39;epatite del mouse, un membro della famiglia Coronaviridae, riproducibile risultati in un&#39;encefalomielite acuta che progredisce verso una malattia demielinizzante cronica. La conseguente neuropatologia durante la fase cronica della malattia &egrave; principalmente immune mediata e simile a quella dell&#39;umana demielinizzante malattia sclerosi multipla. Secrezione di chemochine all&#39;interno del sistema nervoso centrale segnali l&#39;infiltrazione dei leucociti, che si traduce nella distruzione della sostanza bianca e danni neurologici. Il ligando di chemokine CC (CCL) 5 &egrave; localizzato nella sostanza bianca tratti sottoposti a demielinizzazione, suggerendo che questa chemochina partecipa nella patogenesi della malattia, attirando le cellule infiammatorie nel sistema nervoso centrale. In questo studio, abbiamo amministrare un mAb diretto contro CCL5 a topi con demielinizzazione indotta dal virus dell&#39;epatite di mouse stabiliti e compromissione delle abilit&agrave; motorie. Trattamento anti-CCL5 diminuzione delle cellule T accumulo all&#39;interno del SNC, in parte, sulla base virale specificit&agrave; Ag, che indica la capacit&agrave; di modo differenziale destinazione selezionare popolazioni di cellule T. In aggiunta, gestione della funzione neurologica anti-CCL5 migliorato e significativamente (p &lt; o = 0,005) riduce la gravit&agrave; della demielinizzazione e macrofago accumulo all&#39;interno del SNC. Questi risultati dimostrano che la gravit&agrave; della malattia del CNS pu&ograve; essere ridotto attraverso l&#39;uso di un neutralizzante mAb diretto contro CCL5 in un modello virale di demielinizzazione.

Anticorpo targeting del ligand di chemokine CC 5 risultati in infiltrazione leucocitaria diminuita nel sistema nervoso centrale e ridotto la malattia neurologica in un modello di sclerosi multipla virale.

&#x30DE;&#x30A6;&#x30B9;&#x809D;&#x708E;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x3001;&#x30B3;&#x30ED;&#x30CA;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x79D1;&#x30D5;&#x30A1;&#x30DF;&#x30EA;&#x30FC;&#x306E;&#x30E1;&#x30F3;&#x30D0;&#x30FC;&#x3067;&#x3001;&#x6162;&#x6027;&#x306E;&#x8131;&#x9AC4;&#x75BE;&#x60A3;&#x306B;&#x9032;&#x884C;&#x3059;&#x308B;&#x6025;&#x6027;&#x8133;&#x810A;&#x9AC4;&#x708E;&#x306E;&#x518D;&#x73FE;&#x7D50;&#x679C;&#x3068;&#x30DE;&#x30A6;&#x30B9;&#x306E;&#x8133;&#x5185;&#x611F;&#x67D3;&#x3002;&#x75C5;&#x6C17;&#x306E;&#x6162;&#x6027;&#x671F;&#x306E;&#x9593;&#x306B;&#x3001;&#x305D;&#x306E;&#x5F8C;&#x306E;&#x795E;&#x7D4C;&#x75C5;&#x7406;&#x5B66;&#x306F;&#x3001;&#x4E3B;&#x306B;&#x514D;&#x75AB;&#x3068;&#x30D2;&#x30C8;&#x306E;&#x8131;&#x9AC4;&#x75BE;&#x60A3;&#x3001;&#x591A;&#x767A;&#x6027;&#x786C;&#x5316;&#x75C7;&#x306B;&#x4F3C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002; CNS&#x5185;&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3;&#x306E;&#x5206;&#x6CCC;&#x304C;&#x767D;&#x8CEA;&#x3068;&#x795E;&#x7D4C;&#x5B66;&#x7684;&#x969C;&#x5BB3;&#x306E;&#x7834;&#x58CA;&#x3001;&#x305D;&#x306E;&#x7D50;&#x679C;&#x3001;&#x767D;&#x8840;&#x7403;&#x306E;&#x6D78;&#x6F64;&#x3092;&#x3001;&#x901A;&#x77E5;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002; CC&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3;&#x30EA;&#x30AC;&#x30F3;&#x30C9;&#xFF08;CCL&#xFF09;5&#x306F;&#x3001;&#x3053;&#x306E;&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3;&#x306F;&#x3001;CNS&#x3078;&#x306E;&#x708E;&#x75C7;&#x7D30;&#x80DE;&#x3092;&#x8A98;&#x81F4;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x308A;&#x3001;&#x75BE;&#x60A3;&#x306E;&#x75C5;&#x56E0;&#x306B;&#x95A2;&#x4E0E;&#x3057;&#x3066;&#x3044;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3001;&#x8131;&#x9AC4;&#x3092;&#x53D7;&#x3051;&#x3066;&#x3044;&#x308B;&#x767D;&#x8CEA;&#x8DEF;&#x306B;&#x30ED;&#x30FC;&#x30AB;&#x30E9;&#x30A4;&#x30BA;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x672C;&#x7814;&#x7A76;&#x3067;&#x306F;&#x3001;&#x78BA;&#x7ACB;&#x3055;&#x308C;&#x3001;&#x30DE;&#x30A6;&#x30B9;&#x809D;&#x708E;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x8A98;&#x767A;&#x6027;&#x8131;&#x9AC4;&#x3068;&#x904B;&#x52D5;&#x6280;&#x80FD;&#x306E;&#x969C;&#x5BB3;&#x3067;&#x30DE;&#x30A6;&#x30B9;&#x306B;CCL5&#x306B;&#x5BFE;&#x3059;&#x308B;mAb&#x3092;&#x7BA1;&#x7406;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x307E;&#x3059;&#x3002;&#x6297;CCL5&#x6CBB;&#x7642;&#x306F;&#x5DEE;T&#x7D30;&#x80DE;&#x306E;&#x9078;&#x629E;&#x306E;&#x96C6;&#x56E3;&#x3092;&#x5BFE;&#x8C61;&#x3068;&#x3059;&#x308B;&#x80FD;&#x529B;&#x3092;&#x793A;&#x3059;&#x3001;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x306E;Ag&#x7279;&#x7570;&#x6027;&#x3067;&#x3001;&#x90E8;&#x5206;&#x7684;&#x306B;&#x57FA;&#x3065;&#x3044;&#x3066;CNS&#x5185;T&#x7D30;&#x80DE;&#x306E;&#x84C4;&#x7A4D;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x305F;&#x3002;&#x3055;&#x3089;&#x306B;&#x3001;&#x6297;CCL5&#x6539;&#x826F;&#x3055;&#x308C;&#x305F;&#x795E;&#x7D4C;&#x6A5F;&#x80FD;&#x306E;&#x7BA1;&#x7406;&#x3068;&#x6709;&#x610F;&#xFF08;p &#x26;lt;&#x307E;&#x305F;&#x306F;= 0.005&#xFF09;&#x304C;CNS&#x5185;&#x306E;&#x8131;&#x9AC4;&#x304A;&#x3088;&#x3073;&#x30DE;&#x30AF;&#x30ED;&#x30D5;&#x30A1;&#x30FC;&#x30B8;&#x84C4;&#x7A4D;&#x306E;&#x91CD;&#x75C7;&#x5EA6;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x7D50;&#x679C;&#x306F;&#x3001;&#x4E2D;&#x67A2;&#x795E;&#x7D4C;&#x7CFB;&#x306E;&#x75BE;&#x60A3;&#x306E;&#x91CD;&#x75C7;&#x5EA6;&#x306F;&#x3001;&#x8131;&#x9AC4;&#x306E;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x306E;&#x30E2;&#x30C7;&#x30EB;&#x3067;CCL5&#x306B;&#x5BFE;&#x3059;&#x308B;&#x4E2D;&#x548C;&#x30E2;&#x30CE;&#x30AF;&#x30ED;&#x30FC;&#x30CA;&#x30EB;&#x6297;&#x4F53;&#x306E;&#x4F7F;&#x7528;&#x306B;&#x3088;&#x3063;&#x3066;&#x4F4E;&#x6E1B;&#x3067;&#x304D;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;

&#x591A;&#x767A;&#x6027;&#x786C;&#x5316;&#x75C7;&#x306E;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x30E2;&#x30C7;&#x30EB;&#x306E;&#x4E2D;&#x67A2;&#x795E;&#x7D4C;&#x7CFB;&#x304A;&#x3088;&#x3073;&#x795E;&#x7D4C;&#x75BE;&#x60A3;&#x306E;&#x6E1B;&#x5C11;&#x306B;CC&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3;&#x30EA;&#x30AC;&#x30F3;&#x30C9;&#x306E;&#x6E1B;&#x5C11;&#x767D;&#x8840;&#x7403;&#x6D78;&#x6F64;&#x306E;5&#x306E;&#x7D50;&#x679C;&#x3092;&#x6A19;&#x7684;&#x3068;&#x3059;&#x308B;&#x6297;&#x4F53;

Intracerebral &#xAC10;&#xC5FC; &#xC950; &#xB9C8;&#xC6B0;&#xC2A4; &#xD615; &#xAC04;&#xC5FC; &#xBC14;&#xC774;&#xB7EC;&#xC2A4;, Coronaviridae &#xC81C;&#xD488;&#xAD70;&#xC758; &#xC815;&#xC758;&#xC0C1; demyelinating &#xB9CC;&#xC131; &#xC9C8;&#xBCD1;&#xC73C;&#xB85C; &#xC9C4;&#xD589; &#xB418;&#xB294; &#xAE09;&#xC131; encephalomyelitis &#xBC1C;&#xC0DD; &#xD569;&#xB2C8;&#xB2E4;. &#xC9C8;&#xBCD1;&#xC758; &#xB9CC;&#xC131; &#xB2E8;&#xACC4; &#xB4A4;&#xC774;&#xC5B4; neuropathology&#xB294; &#xC8FC;&#xB85C; &#xBA74;&#xC5ED; &#xC911;&#xC7AC; &#xD558; &#xACE0; &#xC778;&#xAC04;&#xC758; demyelinating &#xC9C8;&#xBCD1; &#xB2E4;&#xC911; &#xACBD;&#xD654; &#xC99D; &#xC720;&#xC0AC; &#xD569;&#xB2C8;&#xB2E4;. CNS &#xC548;&#xC5D0;&#xC11C; chemokines&#xC758; &#xBD84; &#xBE44; &#xC2E0;&#xD638; &#xBC31;&#xC0C9; &#xC9C8;&#xACFC; &#xC2E0;&#xACBD; &#xC7A5;&#xC560;&#xC758; &#xD30C;&#xAD34; &#xADC0;&#xCC29;&#xB418;&#xB294; &#xBC31;&#xD608;&#xAD6C;, &#xCE68;&#xD22C;. CC chemokine &#xB9AC;&#xAC04;&#xB4DC; (CCL) 5 &#xBC31; &#xC9C8; &#xCC45;&#xC790; demyelination&#xC774;&#xC774; chemokine CNS&#xB85C; &#xC5FC;&#xC99D; &#xC138;&#xD3EC;&#xB97C; &#xC720;&#xB3C4; &#xD558; &#xC5EC; &#xC9C8;&#xBCD1;&#xC758; &#xBCD1; &#xC778;&#xC5D0; &#xCC38;&#xC5EC; &#xD558;&#xB294; &#xC81C;&#xC548; &#xBC1B;&#xC740; &#xC9C0;&#xC5ED;&#xD654; &#xB429;&#xB2C8;&#xB2E4;. &#xC774; &#xC5F0;&#xAD6C;&#xC5D0;&#xC11C;&#xB294; mAb &#xB9C8;&#xC6B0;&#xC2A4; &#xC124;&#xC815;&#xB41C; &#xB9C8;&#xC6B0;&#xC2A4; &#xAC04;&#xC5FC; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; &#xC720;&#xB3C4; demyelination&#xC640; &#xC7A5;&#xC560;&#xC778;&#xB41C; &#xC6B4;&#xB3D9; &#xB2A5;&#xB825;&#xC744; ccl5&#xC5D0; &#xB300; &#xD55C; &#xAC10;&#xB3C5; &#xAD00;&#xB9AC;. &#xC548;&#xD2F0;-CCL5 &#xCE58;&#xB8CC; CNS &#xB0B4; &#xCD95;&#xC801; &#xAC10;&#xC18C; T &#xC138;&#xD3EC; &#xAE30;&#xBC18;, &#xBD80;&#xBD84;&#xC801;&#xC73C;&#xB85C;, &#xCC28;&#xB3D9; &#xB300;&#xC0C1;&#xC758; &#xB2A5;&#xB825;&#xC744; &#xB098;&#xD0C0;&#xB0B4;&#xB294; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; &#xC131; Ag &#xD2B9;&#xC774;&#xC131;&#xC5D0; T &#xC138;&#xD3EC;&#xC758; &#xC778;&#xAD6C;&#xB97C; &#xC120;&#xD0DD; &#xD569;&#xB2C8;&#xB2E4;. &#xB610;&#xD55C;, &#xAD00;&#xB9AC; &#xAC1C;&#xC120; &#xC548;&#xD2F0; CCL5 &#xC2E0;&#xACBD; &#xAE30;&#xB2A5; &#xBC0F; &#xD604;&#xC800; &#xD558; &#xAC8C; (p &lt; &#xB610;&#xB294; = 0.005) CNS &#xB0B4; demyelination &#xBC0F; macrophage &#xCD95;&#xC801;&#xC758; &#xC2EC;&#xAC01;&#xB3C4; &#xAC10;&#xC18C;. &#xC774;&#xB7EC;&#xD55C; &#xACB0;&#xACFC; &#xC785;&#xC99D; &#xC911;&#xD654; mAb demyelination&#xC758; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; &#xC131; &#xBAA8;&#xB378;&#xC5D0; ccl5&#xC5D0; &#xB300; &#xD55C; &#xAC10;&#xB3C5;&#xC744; &#xD1B5;&#xD574; CNS &#xC9C8;&#xD658;&#xC758; &#xC2EC;&#xAC01;&#xB3C4; &#xC904;&#xC77C; &#xC218; &#xC788;&#xB2E4;.

CC chemokine &#xB9AC;&#xAC04;&#xB4DC; 5&#xC758; &#xD56D; &#xCCB4; &#xD0C0;&#xAC9F;&#xD305; &#xC800;&#xD558; &#xBC31;&#xD608;&#xAD6C; &#xCE68;&#xD22C; &#xC911;&#xC559; &#xC2E0; &#xACBD;&#xACC4;&#xC5D0; &#xBC1C;&#xC0DD; &#xD558; &#xACE0; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; &#xC131; &#xB2E4; &#xBC1C;&#xC131; &#xACBD;&#xD654; &#xC99D; &#xBAA8;&#xB378;&#xC5D0;&#xC11C; &#xC2E0;&#xACBD;&#xD559; &#xC801; &#xC9C8;&#xBCD1;&#xC744; &#xAC10;&#xC18C;.

Infecci&#xF3;n intracerebral de ratones con virus de la hepatitis del rat&#xF3;n, un miembro de la familia Coronaviridae, reproducible resultados en una encefalomielitis aguda que progresa a una enfermedad cr&#xF3;nica desmielinizante. La neuropatolog&#xED;a subsiguiente durante la fase cr&#xF3;nica de la enfermedad es principalmente inmune mediada y similar a la de la esclerosis m&#xFA;ltiple enfermedad desmielinizante humana. La secreci&#xF3;n de quimiocinas en el SNC se&#xF1;ala la infiltraci&#xF3;n de leucocitos, lo que resulta en la destrucci&#xF3;n de la materia blanca y el deterioro neurol&#xF3;gico. El ligando de quimioquinas CC (CCL) 5 se localiza en tractos de sustancia blanca se someten a la desmielinizaci&#xF3;n, sugiriendo que esta quimioquina participa en la patog&#xE9;nesis de la enfermedad mediante la atracci&#xF3;n de c&#xE9;lulas inflamatorias en el SNC. En este estudio, administramos un mAb dirigidos contra CCL5 a los ratones con la hepatitis del rat&#xF3;n establecida inducida por el virus desmielinizaci&#xF3;n y deterioro en las habilidades motoras. Anti-CCL5 tratamiento disminuy&#xF3; la acumulaci&#xF3;n de c&#xE9;lulas T en el SNC basados, en parte, en viral especificidad de Ag, lo que indica la posibilidad de dirigir diferencialmente poblaciones seleccionadas de c&#xE9;lulas T. Adem&#xE1;s, la administraci&#xF3;n de anti-CCL5 la funci&#xF3;n neurol&#xF3;gica y la mejora de forma significativa (p &#x26;lt;o = 0,005) redujo la severidad de la desmielinizaci&#xF3;n y la acumulaci&#xF3;n de macr&#xF3;fagos en el SNC. Estos resultados demuestran que la gravedad de la enfermedad del SNC puede reducirse mediante el uso de un neutralizante AcMo dirigido contra CCL5 en un modelo viral de desmielinizaci&#xF3;n.

Anticuerpos que act&#xFA;an sobre el ligando de quimioquinas CC 5 Resultados de la infiltraci&#xF3;n de leucocitos Disminuci&#xF3;n en el sistema nervioso central y enfermedades neurol&#xF3;gicas reducido en un modelo viral de esclerosis m&#xFA;ltiple

&#x708E;&#x75C7;&#x5728;&#x810A;&#x67F1;&#x810A;&#x9AD3;&#x635F;&#x4F24; (SCI) &#x4E8C;&#x6B21;&#x9000;&#x884C;&#x6027;&#x5E94;&#x5BF9;&#x53D1;&#x6325;&#x5173;&#x952E;&#x7684;&#x4F5C;&#x7528;&#x3002;&#x540E; SCI &#x7684;&#x708E;&#x75C7;&#x7EC6;&#x80DE;&#x7684;&#x5927;&#x91CF;&#x6D8C;&#x5165;&#x7684;&#x524D;&#x9762;&#x6709;&#x7279;&#x5B9A;&#x9AD8;&#x654F;&#xFF0C;&#x5305;&#x62EC;&#x8D8B;&#x5316;&#x56E0;&#x5B50;&#x7684;&#x8868;&#x8FBE;&#x3002;CXCL10 &#x8D8B;&#x5316;&#x56E0;&#x5B50;&#x662F;&#x70C8;&#x6027; T &#x6DCB;&#x5DF4;&#x7EC6;&#x80DE;&#x62DB;&#x8058;&#x4EBA;&#x5458;&#x548C;&#x5F3A;&#x70C8;&#x5377;&#x5165;&#x8BB8;&#x591A;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x75BE;&#x75C5;&#x7684;&#x75C5;&#x7406;&#x3002;&#x6211;&#x4EEC;&#x4EE5;&#x524D;&#x5DF2;&#x7ECF;&#x8868;&#x660E; CXCL10 &#x52A0;&#x5267;&#x4E86;&#x8F85;&#x52A9;&#x53D8;&#x6027;&#xFF0C;&#x901A;&#x8FC7;&#x963B;&#x6B62;&#x524D;&#x8D28;&#x63A7; CXCL10 &#x7684;&#x529F;&#x80FD;&#x5728;&#x8FD9;&#x91CC;&#x6211;&#x4EEC;&#x540E;&#x4EE5;&#x4FBF;&#x8C03;&#x67E5;&#x7F13;&#x548C;&#x540E;&#x6025;&#x6027; SCI &#x7684;&#x7EC4;&#x7EC7;&#x5B66;&#x548C;&#x529F;&#x80FD;&#x8D64;&#x5B57;&#x6B64;&#x6CBB;&#x7597;&#x5E72;&#x9884;&#x7684;&#x6548;&#x679C;&#x548C;&#x8FDB;&#x4E00;&#x6B65;&#x8BC4;&#x4F30;&#x8F85;&#x52A9;&#x53D8;&#x6027;&#x7684; CXCL10 &#x529F;&#x80FD;&#x4F5C;&#x7528;&#x7684;&#x79D1;&#x6280;&#x7BA1;&#x7406;&#x5BF9; CXCL10 1 h &#x7684;&#x4E2D;&#x548C;&#x6297;&#x4F53;&#x3002;&#x4E2D;&#x7684; CXCL10 &#x548C;&#x5927;&#x5927;&#x51CF;&#x5C11;&#x708E;&#x75C7;&#x3001; &#x7EC6;&#x80DE;&#x51CB;&#x4EA1;&#x3001; &#x795E;&#x7ECF;&#x5143;&#x4E22;&#x5931;&#x548C;&#x6574;&#x4E2A;&#x7EC4;&#x7EC7;&#x7684;&#x635F;&#x5931;&#x3002;&#x503C;&#x5F97;&#x6CE8;&#x610F;&#x7684;&#x662F;&#xFF0C;&#x8BE5;&#x6CBB;&#x7597;&#x7684;&#x6CBB;&#x7597;&#x8FD8;&#x63A8;&#x52A8;&#x8840;&#x8FD0;&#x91CD;&#x5EFA;&#x810A;&#x9AD3;&#x635F;&#x4F24;&#x540E;&#x7684;&#x529F;&#x80FD;&#x6062;&#x590D;&#x3002;&#x8FD9;&#x4E9B;&#x6570;&#x636E;&#x8868;&#x660E;&#x6297; CXCL10 &#x6297;&#x4F53;&#x6CBB;&#x7597;&#x662F;&#x6CBB;&#x7597;&#x6025;&#x6027;&#x8D28;&#x63A7;&#x7684;&#x53EF;&#x884C;&#x6218;&#x7565;

&#x6CBB;&#x7597;&#x5931;&#x6548;&#x7684; CXCL10 &#x5728;&#x5C0F;&#x9F20;&#x810A;&#x9AD3;&#x635F;&#x4F24;&#x540E;&#x51CF;&#x5C11;&#x4E86;&#x8F85;&#x52A9;&#x53D8;&#x6027;&#x548C;&#x529F;&#x80FD;&#x7F3A;&#x9677;&#x3002;

Inflammation plays a critical role in the secondary degenerative response to spinal cord injury (SCI). The influx of inflammatory cells following SCI is preceded by the expression of specific chemoattractants, including chemokines. The chemokine CXCL10 is a potent T lymphocyte recruiter and has been strongly implicated in the pathology of many CNS disorders. We have previously demonstrated that CXCL10 exacerbates secondary degeneration by blocking the function of CXCL10 prior to SCI. Here we administered neutralizing antibodies against CXCL10 1 h after SCI in order to investigate the efficacy of this therapeutic intervention in abating histologic and functional deficit following acute SCI and further assess the functional role of CXCL10 in secondary degeneration. Neutralization of CXCL10 significantly reduced inflammation, apoptosis, neuronal loss and whole tissue loss. Notably, this therapeutic treatment also promoted revascularization of the injured spinal cord and functional recovery. These data suggest that anti-CXCL10 antibody treatment is a viable therapeutic strategy for acute SCI.

Therapeutic neutralization of CXCL10 decreases secondary degeneration and functional deficit after spinal cord injury in mice.

L&#x26;#39;inflammation joue un r&#xF4;le crucial dans la r&#xE9;ponse secondaire d&#xE9;g&#xE9;n&#xE9;rative l&#xE9;sion de la moelle &#xE9;pini&#xE8;re (SCI). L&#x26;#39;afflux de cellules inflammatoires &#xE0; la suite SCI est pr&#xE9;c&#xE9;d&#xE9;e par l&#x26;#39;expression de chimio sp&#xE9;cifiques, y compris les chimiokines. La chimiokine CXCL10 est un recruteur de lymphocytes T et puissante a &#xE9;t&#xE9; fortement impliqu&#xE9;e dans la pathologie des troubles du SNC de nombreux. Nous avons d&#xE9;j&#xE0; d&#xE9;montr&#xE9; que CXCL10 exacerbe la d&#xE9;g&#xE9;n&#xE9;rescence secondaire en bloquant la fonction de CXCL10 avant SCI. Ici, nous avons administr&#xE9; des anticorps neutralisants contre le CXCL10 1 h apr&#xE8;s la SCI afin d&#x26;#39;enqu&#xEA;ter sur l&#x26;#39;efficacit&#xE9; de cette intervention th&#xE9;rapeutique dans s&#x26;#39;att&#xE9;nuer d&#xE9;ficit histologique et fonctionnelle &#xE0; la suite aigu&#xEB; SCI et mieux &#xE9;valuer les le r&#xF4;le fonctionnel de CXCL10 dans la d&#xE9;g&#xE9;n&#xE9;rescence secondaire. Neutralisation de CXCL10 consid&#xE9;rablement r&#xE9;duit l&#x26;#39;inflammation, l&#x26;#39;apoptose, la perte neuronale et la perte de tissu ensemble. Notamment, ce traitement th&#xE9;rapeutique a &#xE9;galement favoris&#xE9; la revascularisation de la moelle &#xE9;pini&#xE8;re l&#xE9;s&#xE9;e et la r&#xE9;cup&#xE9;ration fonctionnelle. Ces donn&#xE9;es sugg&#xE8;rent que le traitement d&#x26;#39;anticorps anti-CXCL10 est une strat&#xE9;gie th&#xE9;rapeutique viable pour aigu&#xEB; SCI.

Neutralisation th&#xE9;rapeutique de CXCL10 Diminue la d&#xE9;g&#xE9;n&#xE9;rescence secondaire et du d&#xE9;ficit fonctionnel apr&#xE8;s un traumatisme m&#xE9;dullaire chez la souris

Entz&uuml;ndung spielt eine wichtige Rolle in der sekund&auml;ren degenerativen Reaktion auf Verletzung des R&uuml;ckenmarks (SCI). Der Zustrom von Entz&uuml;ndungszellen nach SCI ist der Ausdruck der spezifischen Attractanten, einschlie&szlig;lich Chemokine vorangestellt. Die Chemokine CXCL10 ist ein potenter T-Lymphozyten-Werber und hat in der Pathologie des vielen CNS St&ouml;rungen stark verwickelt worden. Wir haben bereits bewiesen, dass CXCL10 sekund&auml;ren Entartung versch&auml;rft durch das Blockieren der Funktion der CXCL10 vor Sci. Hier verwaltet wir neutralisierende Antik&ouml;rper gegen CXCL10 1 h nach SCI um untersuchen die Wirksamkeit dieser therapeutische Intervention in abflauende histologische und funktionelle Defizit nach akuten SCI und zudem die funktionale Rolle der CXCL10 im sekund&auml;ren Entartung zu pr&uuml;fen. Neutralisierung des CXCL10 deutlich reduziert, Entz&uuml;ndung, Apoptose, Verlust von Nervenzellen und ganze Gewebe Verlust. Diese therapeutische Behandlung gef&ouml;rdert insbesondere auch Revascularization des verletzten R&uuml;ckenmarks und funktionellen Erholung. Diese Daten legen nahe, dass die Anti-CXCL10 Antik&ouml;rper Behandlung eine tragf&auml;hige therapeutische Strategie f&uuml;r akute Sci.

Therapeutische Neutralisierung des CXCL10 verringert sekund&auml;re Degeneration und funktionelle Defizit nach Verletzung des R&uuml;ckenmarks bei M&auml;usen.

L&#39;infiammazione svolge un ruolo critico nella risposta degenerativa secondaria a lesioni del midollo spinale (SCI). L&#39;afflusso di cellule infiammatorie dopo SCI &egrave; preceduta dall&#39;espressione di chemioattrattanti specifici, tra cui chemiochine. La chemochina CXCL10 &egrave; un reclutatore potente dei linfociti T ed &egrave; stato fortemente implicato nella patologia di molti disturbi del CNS. Abbiamo precedentemente dimostrato che CXCL10 aggrava la degenerazione secondaria bloccando la funzione di CXCL10 prima di SIC. Qui abbiamo somministrato gli anticorpi neutralizzanti contro CXCL10 1 h dopo SCI al fine di indagare l&#39;efficacia di questo intervento terapeutico in cedimento istologica e funzionale deficit seguito SCI acuta e valutare ulteriormente il ruolo funzionale di CXCL10 in degenerazione secondaria. Neutralizzazione del CXCL10 significativamente ridotta infiammazione, apoptosi, perdita di neuroni e tessuto tutta perdita. In particolare, questo trattamento terapeutico promosso anche rivascolarizzazione della ferita del midollo spinale e recupero funzionale. Questi dati suggeriscono che il trattamento dell&#39;anticorpo anti-CXCL10 &egrave; una valida strategia terapeutica per sci acuta.

Terapeutico neutralizzazione del CXCL10 diminuisce degenerazione secondaria e deficit funzionale dopo la ferita del midollo spinale di topi.

&#x708E;&#x75C7;&#x306F;&#x810A;&#x9AC4;&#x640D;&#x50B7;&#xFF08;SCI&#xFF09;&#x3078;&#x306E;&#x4E8C;&#x6B21;&#x5909;&#x6027;&#x53CD;&#x5FDC;&#x306B;&#x304A;&#x3044;&#x3066;&#x91CD;&#x8981;&#x306A;&#x5F79;&#x5272;&#x3092;&#x679C;&#x305F;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002; SCI&#x5F8C;&#x306B;&#x708E;&#x75C7;&#x7D30;&#x80DE;&#x306E;&#x6D41;&#x5165;&#x306F;&#x3001;&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3;&#x3092;&#x542B;&#x3080;&#x7279;&#x5B9A;&#x306E;&#x5316;&#x5B66;&#x8A98;&#x5F15;&#x7269;&#x8CEA;&#x306E;&#x767A;&#x73FE;&#x304C;&#x4ED8;&#x3044;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3;CXCL10&#x306F;&#x3001;&#x5F37;&#x529B;&#x306A;T&#x30EA;&#x30F3;&#x30D1;&#x7403;&#x306E;&#x30EA;&#x30AF;&#x30EB;&#x30FC;&#x30BF;&#x30FC;&#x3067;&#x3042;&#x308B;&#x3068;&#x5F37;&#x304F;&#x591A;&#x304F;&#x306E;&#x4E2D;&#x67A2;&#x795E;&#x7D4C;&#x7CFB;&#x75BE;&#x60A3;&#x306E;&#x75C5;&#x614B;&#x306B;&#x95A2;&#x4E0E;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x6211;&#x3005;&#x306F;&#x4EE5;&#x524D;CXCL10&#x524D;SCI&#x306B;CXCL10&#x306E;&#x6A5F;&#x80FD;&#x3092;&#x30D6;&#x30ED;&#x30C3;&#x30AF;&#x3059;&#x308B;&#x3053;&#x3068;&#x306B;&#x3088;&#x308A;&#x3001;&#x4E8C;&#x6B21;&#x5909;&#x6027;&#x3092;&#x60AA;&#x5316;&#x3055;&#x305B;&#x308B;&#x3053;&#x3068;&#x3092;&#x5B9F;&#x8A3C;&#x3057;&#x305F;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x6025;&#x6027;SCI&#x5F8C;&#x306B;&#x7D44;&#x7E54;&#x5B66;&#x7684;&#x304A;&#x3088;&#x3073;&#x6A5F;&#x80FD;&#x7684;&#x306A;&#x8D64;&#x5B57;&#x3092;&#x8870;&#x3048;&#x308B;&#x3053;&#x306E;&#x6CBB;&#x7642;&#x7684;&#x4ECB;&#x5165;&#x306E;&#x6709;&#x52B9;&#x6027;&#x3092;&#x8ABF;&#x67FB;&#x3057;&#x3001;&#x3055;&#x3089;&#x306B;&#x4E8C;&#x6B21;&#x5909;&#x6027;&#x306B;CXCL10&#x306E;&#x6A5F;&#x80FD;&#x7684;&#x5F79;&#x5272;&#x3092;&#x8A55;&#x4FA1;&#x3059;&#x308B;&#x305F;&#x3081;&#x306B;&#x3001;SCI&#x5F8C;&#x306E;CXCL10 1&#x6642;&#x9593;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x4E2D;&#x548C;&#x6297;&#x4F53;&#x3092;&#x6295;&#x4E0E;&#x3057;&#x305F;&#x3002; CXCL10&#x5927;&#x5E45;&#x306B;&#x6E1B;&#x5C11;&#x3057;&#x3001;&#x708E;&#x75C7;&#x3001;&#x30A2;&#x30DD;&#x30C8;&#x30FC;&#x30B7;&#x30B9;&#x3001;&#x795E;&#x7D4C;&#x7D30;&#x80DE;&#x306E;&#x640D;&#x5931;&#x3068;&#x5168;&#x4F53;&#x306E;&#x7D44;&#x7E54;&#x306E;&#x640D;&#x5931;&#x306E;&#x4E2D;&#x548C;&#x3002;&#x7279;&#x306B;&#x3001;&#x3053;&#x306E;&#x6CBB;&#x7642;&#x306F;&#x307E;&#x305F;&#x3001;&#x810A;&#x9AC4;&#x640D;&#x50B7;&#x3068;&#x6A5F;&#x80FD;&#x56DE;&#x5FA9;&#x306E;&#x8840;&#x884C;&#x3092;&#x4FC3;&#x9032;&#x3057;&#x305F;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x30C7;&#x30FC;&#x30BF;&#x306F;&#x3001;&#x6297;CXCL10&#x6297;&#x4F53;&#x6CBB;&#x7642;&#x306F;&#x3001;&#x6025;&#x6027;SCI&#x306E;&#x305F;&#x3081;&#x306E;&#x5B9F;&#x884C;&#x53EF;&#x80FD;&#x306A;&#x6CBB;&#x7642;&#x6226;&#x7565;&#x3067;&#x3042;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x5506;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;

CXCL10&#x306E;&#x6CBB;&#x7642;&#x306E;&#x4E2D;&#x548C;&#x306F;&#x3001;&#x30DE;&#x30A6;&#x30B9;&#x306E;&#x810A;&#x9AC4;&#x640D;&#x50B7;&#x5F8C;&#x306E;&#x4E8C;&#x6B21;&#x5909;&#x6027;&#x3068;&#x6A5F;&#x80FD;&#x969C;&#x5BB3;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x308B;

&#xC5FC;&#xC99D; &#xBCF4;&#xC870; &#xD1F4;&#xD589; &#xC131; &#xCC99;&#xC218; &#xC0C1;&#xD574; (SCI)&#xC5D0; &#xB300; &#xD55C; &#xC751;&#xB2F5;&#xC5D0;&#xC11C; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xD55C;&#xB2E4;. SCI &#xB2E4;&#xC74C;&#xACFC; &#xAC19;&#xC740; &#xC5FC;&#xC99D; &#xC131; &#xC138;&#xD3EC;&#xC758; &#xC720;&#xC785;&#xC740; chemokines &#xB4F1; &#xD2B9;&#xC815; chemoattractants&#xC758; &#xC2DD;&#xC5D0; &#xC758;&#xD574; &#xC55E;&#xC5D0; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. Chemokine CXCL10 &#xAC15;&#xB825;&#xD55C; T &#xB9BC;&#xD504; &#xAD6C; &#xBAA8;&#xC9D1; &#xC774;&#xBA70; &#xB9CE;&#xC740; CNS &#xC9C8;&#xD658;&#xC758; &#xBCD1; &#xB9AC;&#xC5D0; &#xAC15;&#xB825; &#xD558; &#xAC8C; &#xC5F0;&#xB8E8; &#xB418;&#xC5B4; &#xC788;&#xB2E4;. &#xC6B0;&#xB9AC;&#xB294; &#xC774;&#xC804;&#xC5D0; CXCL10 CXCL10 &#xC774;&#xC804;&#xC5D0; &#xACFC;&#xD559;&#xC758; &#xAE30;&#xB2A5;&#xC744; &#xCC28;&#xB2E8; &#xD558; &#xC5EC; 2 &#xCC28; &#xBCC0;&#xC131;&#xC744; &#xC545;&#xD654; &#xC99D;&#xBA85; &#xD558;&#xACE0;&#xC788;&#xB2E4; &#xC5EC;&#xAE30; &#xC6B0;&#xB9AC; &#xBB38;&#xD654;&#xC5D0; &#xB530;&#xB77C; &#xAE09;&#xC131; SCI &#xC870;&#xC9C1;&#xD559; &#xBC0F; &#xAE30;&#xB2A5;&#xC801;&#xC778; &#xC801;&#xC790;&#xB97C; &#xAC10;&#xC18C; &#xC2DC;&#xD0A4;&#xACE0;&#xC774; &#xCE58;&#xB8CC; &#xC801; &#xAC1C;&#xC785;&#xC758; &#xD6A8;&#xB2A5;&#xC744; &#xC870;&#xC0AC; &#xD558; &#xACE0; &#xCD94;&#xAC00; 2 &#xCC28; &#xBCC0;&#xC131;&#xC5D0; cxcl10&#xC758; &#xAE30;&#xB2A5;&#xC801; &#xC5ED;&#xD560;&#xC744; &#xD3C9;&#xAC00; &#xD6C4; CXCL10 1 h&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xD654; &#xD56D; &#xCCB4;&#xB97C; &#xAD00;&#xB9AC;. Cxcl10&#xC758; &#xC911;&#xB9BD;&#xD654;&#xB294; &#xD06C;&#xAC8C; &#xC5FC;&#xC99D;, apoptosis, &#xC2E0;&#xACBD; &#xC190;&#xC2E4;&#xACFC; &#xC804;&#xCCB4; &#xC870;&#xC9C1; &#xC190;&#xC2E4; &#xAC10;&#xC18C;. &#xD2B9;&#xD788;,&#xC774; &#xCE58;&#xB8CC; &#xCE58;&#xB8CC;&#xB294; &#xB610;&#xD55C; &#xC190;&#xC0C1;&#xB41C; &#xCC99;&#xC218; &#xBC0F; &#xAE30;&#xB2A5; &#xBCF5;&#xAD6C; revascularization &#xC2B9;&#xC9C4;. &#xC774;&#xB7EC;&#xD55C; &#xB370;&#xC774;&#xD130; &#xC548;&#xD2F0;-CXCL10 &#xD56D; &#xCCB4; &#xCE58;&#xB8CC;&#xB294; &#xAE09;&#xC131; &#xACFC;&#xD559;&#xC5D0; &#xB300; &#xD55C; &#xAC00;&#xB2A5;&#xD55C; &#xCE58;&#xB8CC; &#xC804;&#xB7B5; &#xC81C;&#xC548;

Cxcl10&#xC758; &#xCE58;&#xB8CC; &#xC911;&#xD654; &#xC950;&#xC5D0;&#xC11C; &#xCC99;&#xC218; &#xC190;&#xC0C1; &#xD6C4; 2 &#xCC28; &#xBCC0;&#xC131; &#xBC0F; &#xAE30;&#xB2A5; &#xC801; &#xC790;&#xAC00; &#xAC10;&#xC18C;&#xD569;&#xB2C8;&#xB2E4;.

La inflamaci&#xF3;n desempe&#xF1;a un papel cr&#xED;tico en la respuesta secundaria a una lesi&#xF3;n degenerativa de la m&#xE9;dula espinal (SCI). El influjo de c&#xE9;lulas inflamatorias despu&#xE9;s de SCI es precedido por la expresi&#xF3;n de factores quimiot&#xE1;cticos espec&#xED;ficos, como las quimiocinas. Las quimioquinas CXCL10 es un potente reclutador de los linfocitos T y ha sido fuertemente implicados en la patolog&#xED;a de muchas enfermedades del SNC. Hemos demostrado anteriormente que CXCL10 exacerba la degeneraci&#xF3;n secundaria mediante el bloqueo de la funci&#xF3;n de CXCL10 antes de la SCI. Aqu&#xED; se administr&#xF3; anticuerpos neutralizantes contra la CXCL10 1 hora despu&#xE9;s de la lesi&#xF3;n con el fin de investigar la eficacia de esta intervenci&#xF3;n terap&#xE9;utica en el abatimiento del d&#xE9;ficit histol&#xF3;gica y funcional despu&#xE9;s de SCI aguda y evaluar mejor el papel funcional de CXCL10 en la degeneraci&#xF3;n secundaria. La neutralizaci&#xF3;n de CXCL10 reduce significativamente la inflamaci&#xF3;n, apoptosis, p&#xE9;rdida neuronal y la p&#xE9;rdida de todo el tejido. En particular, este tratamiento terap&#xE9;utico tambi&#xE9;n promovi&#xF3; la revascularizaci&#xF3;n de la m&#xE9;dula espinal lesionada y la recuperaci&#xF3;n funcional. Estos datos sugieren que el anti-CXCL10 tratamiento con el anticuerpo es una estrategia terap&#xE9;utica viable para la lesi&#xF3;n medular aguda.

La neutralizaci&#xF3;n de CXCL10 terap&#xE9;utica disminuye la degeneraci&#xF3;n secundaria y d&#xE9;ficit funcional despu&#xE9;s de una lesi&#xF3;n de la m&#xE9;dula espinal en ratones

CC &#x8D8B;&#x5316;&#x56E0;&#x5B50;&#x53D7;&#x4F53; 1 (CCR1) &#x4E3B;&#x673A;&#x9632;&#x5FA1;&#x548C;&#x75BE;&#x75C5;&#x53D1;&#x5C55;&#x4E2D;&#x7684;&#x4F5C;&#x7528;&#x786E;&#x5B9A;&#x5728;&#x6A21;&#x578B;&#x4E2D;&#x7684;&#x75C5;&#x6BD2;&#x5F15;&#x8D77;&#x7684;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x75BE;&#x75C5;&#x3002;&#x8111;&#x51FA;&#x8840; (IC) &#x611F;&#x67D3;&#x7684;&#x5C0F;&#x9F20;&#x5C0F;&#x9F20;&#x809D;&#x708E;&#x75C5;&#x6BD2; &#xFF08;MHV&#xFF09; &#x4F1A;&#x5BFC;&#x81F4;&#x75BE;&#x75C5;&#x591A;&#x53D1;&#x6027;&#x786C;&#x5316; (MS) &#x540E;&#x8DDF;&#x7684;&#x7C7B;&#x4F3C;&#x75C5;&#x7406;&#x5B66;&#x6162;&#x6027;&#x8131;&#x9AD3;&#x9798;&#x75BE;&#x75C5;&#x6025;&#x6027;&#x8111;&#x708E;&#x3002;&#x6CA1;&#x6709;&#x6B7B;&#x4EA1;&#x7387;&#x4E0A;&#x5347;&#x540E;&#x7684;&#x5C0F;&#x9F20;&#x7F3A;&#x4E4F; CCR1 MHV &#x611F;&#x67D3;&#x75C5;&#x6025;&#x6027;&#x671F; (CCR1-/-) &#x4E0E;&#x91CE;&#x751F;&#x578B;&#x76F8;&#x6BD4; (CCR1 + / +) &#x5C0F;&#x9F20;&#x3002;&#x7136;&#x800C;&#xFF0C;&#x7531; 21 d &#x4E0E;&#x53D7;&#xFF0C;74%&#x7684; CCR1/&#x5C0F;&#x9F20;&#x5DF2;&#x7ECF;&#x5C48;&#x670D;&#x6B7B;&#x4EA1;&#x76F8;&#x6BD4;&#xFF0C;&#x53EA;&#x6709; 32%&#x6B7B;&#x4EA1;&#x7387;&#x7684; CCR1 + + &#x5C0F;&#x9F20;&#xFF0C;&#x6307;&#x793A;&#x4FE1;&#x53F7;&#x901A;&#x8FC7; CCR1 &#x5927;&#x5927;&#x7684;&#x8D8B;&#x5316;&#x56E0;&#x5B50; (p &lt; &#x6216; = 0.04) &#x589E;&#x5F3A;&#x751F;&#x5B58;&#x4E4B;&#x540E; MHV IC &#x611F;&#x67D3;&#x3002;CCR1/&#x5C0F;&#x9F20;&#x7684;&#x6B7B;&#x4EA1;&#x7387;&#x589E;&#x52A0;&#x4E0D;&#x662F;&#x4E0E;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#xFF0C;&#x4ECE;&#x589E;&#x52A0;&#x75C5;&#x6BD2;&#x6062;&#x590D;&#x5173;&#x8054;&#x867D;&#x7136; CCR1 &#x865A;&#x4E0E;&#x76F8;&#x5173;&#x51CF;&#x5C11; T &#x7EC6;&#x80DE;&#x5728;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x5185;&#x79EF;&#x805A;&#x5C16;&#x9510;&#xFF0C;&#x800C;&#x4E0D;&#x662F;&#x6162;&#x6027;&#x7684;&#x75BE;&#x75C5;&#x3002;T &#x7EC6;&#x80DE;&#x5728;&#x6025;&#x6027;&#x75BE;&#x75C5;&#x671F;&#x95F4;&#x8D29;&#x5356;&#x5230; CCR1/&#x5C0F;&#x9F20;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x51CF;&#x5C11;&#xFF0C;&#x5C3D;&#x7BA1;&#x4E3B;&#x673A;&#x9632;&#x5FA1;&#x7EC4;&#x4EF6;&#x4FDD;&#x6301;&#x4E0D;&#x53D8; &#xFF1B;T &#x7EC6;&#x80DE;&#x6548;&#x5E94;&#x804C;&#x80FD;&#x5305;&#x62EC;&#x6EB6;&#x6D3B;&#x6027;&#x548C;&#x589E;&#x6B96;&#x548C;&#x5E72;&#x6270;&#x7D20; &gamma; &#x5728;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x5185;&#x7684;&#x8868;&#x8FBE;&#x4E0D;&#x662F;&#x5927;&#x5927;&#x4E0D;&#x540C;&#x4E4B;&#x95F4; CCR1 + + &#x548C; CCR1-/-&#x611F;&#x67D3;&#x5C0F;&#x9F20;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x5DE8;&#x566C;&#x7EC6;&#x80DE;&#x6D78;&#x6DA6;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x5E76;&#x6CA1;&#x6709;&#x53D7;&#x5230;&#x5F71;&#x54CD; MHV &#x611F;&#x67D3; CCR1-/-&#x5C0F;&#x9F20;&#x76F8;&#x6BD4; CCR1 + + &#x5C0F;&#x9F20;&#x3002;&#x6B64;&#x5916;&#xFF0C;&#x795E;&#x7ECF;&#x75C5;&#x7406;&#x5B66;&#x8BC4;&#x4F30;&#x663E;&#x793A;&#x8131;&#x9AD3;&#x9798; CCR1 &#x7F3A;&#x9677;&#x578B;&#x548C;&#x91CE;&#x751F;&#x578B;&#x5C0F;&#x9F20;&#x4E4B;&#x95F4;&#x7684;&#x4E25;&#x91CD;&#x6027;&#x6CA1;&#x6709;&#x5DEE;&#x522B;&#x3002;&#x5728;&#x4E00;&#x8D77;&#xFF0C;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x663E;&#x793A; T &#x7EC6;&#x80DE;&#x548C;&#x5DE8;&#x566C;&#x7EC6;&#x80DE;&#x8D29;&#x8FD0;&#x4E0D;&#x4F9D;&#x8D56; CCR1 &#x548C;&#x7A81;&#x51FA; CCR1 &#x4FE1;&#x53F7;&#x5728;&#x4FC3;&#x8FDB;&#x751F;&#x5B58; MHV &#x6162;&#x6027;&#x611F;&#x67D3;&#x671F;&#x95F4;&#x53D1;&#x6325;&#x91CD;&#x8981;&#x4F5C;&#x7528;&#x3002;

CCR1 &#x7F3A;&#x9677;&#x589E;&#x52A0;&#x5BF9;&#x4E2D;&#x67A2;&#x795E;&#x7ECF;&#x7CFB;&#x7EDF;&#x7684;&#x81F4;&#x547D;&#x7684;&#x51A0;&#x72B6;&#x75C5;&#x6BD2;&#x611F;&#x67D3;&#x7684;&#x6613;&#x611F;&#x6027;&#x3002;

The role of CC chemokine receptor 1 (CCR1) in host defense and disease development was determined in a model of viral-induced neurologic disease. Intracerebral (IC) infection of mice with mouse hepatitis virus (MHV) results in an acute encephalitis followed by a chronic demyelinating disease similar in pathology to the disease multiple sclerosis (MS). No increase in mortality was observed during the acute phase of disease following MHV infection of mice lacking CCR1 (CCR1-/-) as compared to wild-type (CCR1+/+) mice. However, by 21 d post-infection, 74% of CCR1-/- mice had succumbed to death compared to only 32% mortality of CCR1+/+ mice, indicating that chemokine signaling through CCR1 significantly (p <or= 0.04) enhanced survival following IC infection with MHV. Increased mortality in CCR1-/- mice was not associated with increased viral recovery from the CNS, although CCR1 deficiency correlated with reduced T-cell accumulation within the CNS during acute, but not chronic, disease. Despite the reduction in T-cell trafficking into the CNS of CCR1-/- mice during acute disease, components of host defense remained unaltered; T-cell effector functions including cytolytic activity and proliferation and the expression of IFN-gamma within the CNS were not significantly different between CCR1+/+ and CCR1-/- infected mice. In addition, macrophage infiltration into the CNS was unaffected in MHV-infected CCR1-/- mice when compared to CCR1+/+ mice. Furthermore, assessment of neuropathology revealed no difference in the severity of demyelination between CCR1-deficient and wild-type mice. Together, these findings reveal that T-cell and macrophage trafficking are not dependent on CCR1 and highlight an important role for CCR1 signaling in promoting survival during chronic MHV infection.

CCR1 deficiency increases susceptibility to fatal coronavirus infection of the central nervous system.

Le r&#xF4;le de r&#xE9;cepteur de chimiokine CC 1 (CCR1) en d&#xE9;fense de l&#x26;#39;h&#xF4;te et d&#xE9;veloppement de la maladie a &#xE9;t&#xE9; d&#xE9;termin&#xE9;e dans un mod&#xE8;le d&#x26;#39;origine virale induite par une maladie neurologique. Intrac&#xE9;r&#xE9;brale (IC) infection de la souris avec la souris virus de l&#x26;#39;h&#xE9;patite (MHV) se traduit par une enc&#xE9;phalite aigu&#xEB; suivie d&#x26;#39;une maladie d&#xE9;my&#xE9;linisante chronique similaire dans la pathologie de la maladie de la scl&#xE9;rose multiple (MS). Pas d&#x26;#39;augmentation de la mortalit&#xE9; a &#xE9;t&#xE9; observ&#xE9;e au cours de la phase aigu&#xEB; de la maladie suite &#xE0; une infection des souris d&#xE9;pourvues de MHV CCR1 (CCR1-/ -) par rapport &#xE0; la souche sauvage (CCR1 + / +) chez la souris. Toutefois, avant le 21 d post-infection, 74% des CCR1-/ - souris avaient succomb&#xE9; &#xE0; la mort par rapport &#xE0; seulement 32% de mortalit&#xE9; des CCR1 souris + / +, ce qui indique que la signalisation par la chimiokine CCR1 de fa&#xE7;on significative (p &#x3C;or= 0.04) enhanced survival following IC infection with MHV. Increased mortality in CCR1-/- mice was not associated with increased viral recovery from the CNS, although CCR1 deficiency correlated with reduced T-cell accumulation within the CNS during acute, but not chronic, disease. Despite the reduction in T-cell trafficking into the CNS of CCR1-/- mice during acute disease, components of host defense remained unaltered; T-cell effector functions including cytolytic activity and proliferation and the expression of IFN-gamma within the CNS were not significantly different between CCR1+/+ and CCR1-/- infected mice. In addition, macrophage infiltration into the CNS was unaffected in MHV-infected CCR1-/- mice when compared to CCR1+/+ mice. Furthermore, assessment of neuropathology revealed no difference in the severity of demyelination between CCR1-deficient and wild-type mice. Together, these findings reveal that T-cell and macrophage trafficking are not dependent on CCR1 and highlight an important role for CCR1 signaling in promoting survival during chronic MHV infection.

D&#xE9;ficit CCR1 augmente la susceptibilit&#xE9; &#xE0; l&#x26;#39;infection coronavirus fatale du syst&#xE8;me nerveux central

Die Rolle der CC-Chemokine-Rezeptor 1 (CCR1) Host Verteidigung und Krankheit Entwicklung wurde in einem Modell der viral-induzierte neurologische Krankheit bestimmt. Intrazerebrale (IC)-Infektion der M&auml;use mit Maus-Hepatitis-Virus (MHV) f&uuml;hrt eine akute Enzephalitis, gefolgt von einer chronischen demyelinisierende Erkrankung, die &auml;hnlich in der Pathologie in die Krankheit Multiple Sklerose (MS). Keine Zunahme der Mortalit&auml;t wurde w&auml;hrend der akuten Phase der Krankheit nach MHV-Infektion von M&auml;usen fehlt CCR1 beobachtet (CCR1-/-) im Vergleich zu Wildtyp (CCR1 + / +) M&auml;use. Jedoch durch 21d Stunden, 74 % der CCR1-/-M&auml;use hatte erlagen Tod im Vergleich zu nur 32 % Mortalit&auml;t von CCR1 + / + M&auml;use, angibt, dass Chemokine Signalisierung durch CCR1 erheblich (p &lt; oder = 0,04) verbessert &Uuml;berleben nach IC-Infektion mit MHV. Erh&ouml;hte Sterblichkeit bei CCR1-/-M&auml;usen wurde nicht erh&ouml;hte virale Erholung von der CNS, zugeordnet, obwohl CCR1 Mangel korreliert mit T-Zell-Ansammlung innerhalb des CNS w&auml;hrend akuter, aber nicht chronische Krankheit reduziert. Trotz der Verringerung der T-Zell-Verschleppung nach dem CNS von CCR1-/-M&auml;usen w&auml;hrend der akuten Krankheit blieben die Bestandteile der Host Verteidigung unver&auml;ndert; T-Zell-Effektor-Funktionen einschlie&szlig;lich CYTOLYTISCHE Aktivit&auml;t und Vermehrung und die Expression von IFN-Gamma innerhalb des CNS waren nicht signifikant unterschiedlich zwischen CCR1 + / + und CCR1-/-M&auml;usen infiziert. Dar&uuml;ber hinaus Makrophagen Infiltration in der CNS verschont MHV-infizierten CCR1-/-M&auml;usen im Vergleich zu CCR1 + / + M&auml;use. Dar&uuml;ber hinaus ergab die Beurteilung der Neuropathologie keinen Unterschied in der Schwere der Demyelinisierung zwischen CCR1-defizienten und Wildtyp M&auml;usen. Zusammen, zeigen diese Erkenntnisse, dass T-Zellen und Makrophagen Menschenhandel nicht abh&auml;ngig von CCR1 sind und markieren Sie eine wichtige Rolle f&uuml;r CCR1 Signalisierung bei der F&ouml;rderung von &uuml;berleben w&auml;hrend der chronischen Infektion des MHV.

CCR1-Mangel erh&ouml;ht die Anf&auml;lligkeit f&uuml;r fatal Coronavirus-Infektion des zentralen Nervensystems.

Il ruolo della CC chemokine receptor 1 (CCR1) nello sviluppo di malattia e difesa ospite &egrave; stato determinato in un modello di malattia neurologica virale indotta. Infezione (IC) intracerebrale di topi con il virus dell&#39;epatite del mouse (MHV) si traduce in un&#39;encefalite acuta, seguita da una malattia demielinizzante cronica simile in patologia per la malattia sclerosi a placche (MS). &Egrave; stato osservato alcun aumento della mortalit&agrave; durante la fase acuta della malattia dopo infezione MHV di topi privi di CCR1 (CCR1-/-) rispetto al wild-type (CCR1 + +) topi. Tuttavia, da post-infection d 21, 74% di CCR1-/-mice aveva ceduto alla morte rispetto al solo 32% mortalit&agrave; di CCR1 + + topi, indicando che chemokine segnalazione attraverso CCR1 significativamente (p &lt; o = 0,04) migliorata sopravvivenza dopo infezione IC con MHV. Aumento della mortalit&agrave; in CCR1-/-mice non era associato con maggiore recupero virale dal sistema nervoso centrale, anche se deficit CCR1 correlato con ridotto accumulo di cellule T all&#39;interno del SNC durante la malattia acuta, ma non cronico. Nonostante la riduzione di traffico in SNC di CCR1-/-mice durante la malattia acuta delle cellule T, componenti della difesa ospite &egrave; rimasto inalterati; Funzioni effettrici delle cellule T compreso attivit&agrave; citolitica e la proliferazione e l&#39;espressione di IFN-gamma all&#39;interno del SNC non erano significativamente differenti tra CCR1 + + e CCR1-/-infettati topi. Inoltre, infiltrazione dei macrofagi nel sistema nervoso centrale &egrave; stato inalterato in MHV-infettati CCR1-/-mice rispetto a CCR1 + + topi. Inoltre, la valutazione di Neuropatologia non rivelato alcuna differenza nella gravit&agrave; della demielinizzazione tra topi CCR1-carenti e wild-type. Insieme, questi risultati rivelano che delle cellule T e macrofagi traffico non sono dipendenti da CCR1 ed evidenziare un ruolo importante per CCR1 segnalazione nel promuovere la sopravvivenza durante l&#39;infezione cronica MHV.

CCR1 deficit aumenta la suscettibilit&agrave; all&#39;infezione da coronavirus irreversibile del sistema nervoso centrale.

&#x5BBF;&#x4E3B;&#x9632;&#x5FA1;&#x3068;&#x75BE;&#x60A3;&#x767A;&#x75C7;&#x306B;&#x304A;&#x3051;&#x308B;CC&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3;&#x53D7;&#x5BB9;&#x4F53;1&#xFF08;CCR1&#xFF09;&#x306E;&#x5F79;&#x5272;&#x306F;&#x3001;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x8A98;&#x767A;&#x6027;&#x795E;&#x7D4C;&#x75BE;&#x60A3;&#x306E;&#x30E2;&#x30C7;&#x30EB;&#x3067;&#x6C7A;&#x5B9A;&#x3055;&#x308C;&#x305F;&#x3002;&#x75C5;&#x7406;&#x5B66;&#x306E;&#x75C5;&#x6C17;&#x591A;&#x767A;&#x6027;&#x786C;&#x5316;&#x75C7;&#xFF08;MS&#xFF09;&#x306B;&#x4F3C;&#x3066;&#x6162;&#x6027;&#x8131;&#x9AC4;&#x75BE;&#x60A3;&#x306B;&#x7D9A;&#x3044;&#x3066;&#x6025;&#x6027;&#x8133;&#x708E;&#x306E;&#x30DE;&#x30A6;&#x30B9;&#x809D;&#x708E;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#xFF08;MHV&#xFF09;&#x306E;&#x7D50;&#x679C;&#x3068;&#x30DE;&#x30A6;&#x30B9;&#x306E;&#x8133;&#x5185;&#xFF08;IC&#xFF09;&#x306E;&#x611F;&#x67D3;&#x3002;&#x91CE;&#x751F;&#x578B;&#xFF08;CCR1 + / +&#xFF09;&#x30DE;&#x30A6;&#x30B9;&#x3068;&#x6BD4;&#x8F03;&#x3057;&#x3066; - &#x6B7B;&#x4EA1;&#x7387;&#x306E;&#x5897;&#x52A0;&#x306F;CCR1&#x3092;&#xFF08;CCR1-/&#xFF09;&#x6B20;&#x640D;&#x30DE;&#x30A6;&#x30B9;&#x306E;MHV&#x611F;&#x67D3;&#x5F8C;&#x306E;&#x75BE;&#x60A3;&#x306E;&#x6025;&#x6027;&#x671F;&#x306B;&#x89B3;&#x5BDF;&#x3055;&#x308C;&#x306A;&#x304B;&#x3063;&#x305F;&#x3002;&#x3057;&#x304B;&#x3057;&#x3001;21 d&#x306E;&#x5F8C;&#x306E;&#x611F;&#x67D3;&#x306B;&#x3088;&#x3063;&#x3066;&#x3001;CCR1-/&#x306E;74&#xFF05; - &#x30DE;&#x30A6;&#x30B9;&#x3067;&#x306F;&#x3001;&#x30B1;&#x30E2;&#x30AB;&#x30A4;&#x30F3;&#x306F;&#x3001;&#xFF08;P&#x5927;&#x5E45;&#x306B;CCR1&#x3092;&#x4ECB;&#x3057;&#x305F;&#x30B7;&#x30B0;&#x30CA;&#x30EB;&#x3092;&#x793A;&#x3057;&#x3001;CCR1 + / +&#x30DE;&#x30A6;&#x30B9;&#x306E;&#x308F;&#x305A;&#x304B;32&#xFF05;&#x306E;&#x6B7B;&#x4EA1;&#x7387;&#x306B;&#x6BD4;&#x3079;&#x3066;&#x6B7B;&#x306B;&#x5C48;&#x3057;&#x305F;&#x3C;or= 0.04) enhanced survival following IC infection with MHV. Increased mortality in CCR1-/- mice was not associated with increased viral recovery from the CNS, although CCR1 deficiency correlated with reduced T-cell accumulation within the CNS during acute, but not chronic, disease. Despite the reduction in T-cell trafficking into the CNS of CCR1-/- mice during acute disease, components of host defense remained unaltered; T-cell effector functions including cytolytic activity and proliferation and the expression of IFN-gamma within the CNS were not significantly different between CCR1+/+ and CCR1-/- infected mice. In addition, macrophage infiltration into the CNS was unaffected in MHV-infected CCR1-/- mice when compared to CCR1+/+ mice. Furthermore, assessment of neuropathology revealed no difference in the severity of demyelination between CCR1-deficient and wild-type mice. Together, these findings reveal that T-cell and macrophage trafficking are not dependent on CCR1 and highlight an important role for CCR1 signaling in promoting survival during chronic MHV infection.

CCR1&#x6B20;&#x640D;&#x306F;&#x4E2D;&#x67A2;&#x795E;&#x7D4C;&#x7CFB;&#x306E;&#x81F4;&#x547D;&#x7684;&#x306A;&#x30B3;&#x30ED;&#x30CA;&#x30A6;&#x30A4;&#x30EB;&#x30B9;&#x611F;&#x67D3;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x611F;&#x53D7;&#x6027;&#x3092;&#x5897;&#x52A0;&#x3055;&#x305B;&#x308B;

CC chemokine &#xC218;&#xC6A9; &#xCCB4; 1 (CCR1) &#xD638;&#xC2A4;&#xD2B8; &#xBC29;&#xC5B4;&#xC640; &#xC9C8;&#xBCD1; &#xAC1C;&#xBC1C;&#xC5D0;&#xC11C;&#xC758; &#xC5ED;&#xD560;&#xC740; &#xC2E0;&#xACBD;&#xD559; &#xC801; &#xC9C8;&#xBCD1; &#xC720;&#xBC1C; &#xBC14;&#xC774;&#xB7EC;&#xC2A4;&#xC758; &#xBAA8;&#xB378;&#xC5D0;&#xC11C; &#xACB0;&#xC815; &#xD588;&#xB2E4;. &#xB9C8;&#xC6B0;&#xC2A4; &#xD615; &#xAC04;&#xC5FC; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; (MHV) &#xC0DD;&#xC950;&#xC758; intracerebral (IC) &#xAC10;&#xC5FC; &#xC9C8;&#xD658; &#xB2E4; &#xBC1C;&#xC131; &#xACBD;&#xD654; &#xC99D; (MS)&#xB97C; &#xB9CC;&#xC131; demyelinating &#xC9C8;&#xBCD1; &#xBCD1;&#xB9AC;&#xD559;&#xC5D0;&#xC11C; &#xBE44;&#xC2B7;&#xD55C; &#xB4A4; &#xAE09;&#xC131; &#xB1CC;&#xC5FC; &#xBC1C;&#xC0DD; &#xD569;&#xB2C8;&#xB2E4;. &#xC0AC;&#xB9DD;&#xB960;&#xC758; &#xC99D;&#xAC00; CCR1 &#xBD80;&#xC871; &#xD55C; &#xC950;&#xC758; MHV &#xAC10;&#xC5FC;&#xC5D0; &#xB530;&#xB77C; &#xC9C8;&#xBCD1;&#xC758; &#xAE09;&#xC131; &#xB2E8;&#xACC4; &#xB3D9;&#xC548; &#xAD00;&#xCC30; &#xB418;&#xC5C8;&#xB2E4; (CCR1-/-) &#xC57C;&#xC0DD;-&#xD0C0;&#xC785;&#xC5D0; &#xBE44;&#xD574; (CCR1 + +) &#xC950;. &#xADF8;&#xB7EC;&#xB098; 21 d post-infection, CCR1/&#xC950;&#xC758; 74 %ccr1 &#xC720;&#xC77C;&#xD55C; 32% &#xC0AC;&#xB9DD;&#xB960;&#xC5D0; &#xBE44;&#xD574; &#xC8FD;&#xC74C;&#xC5D0; &#xAD74;&#xBCF5; &#xD588;&#xB2E4; + + ccr1&#xB97C; &#xD1B5;&#xD574; &#xD06C;&#xAC8C; &#xC2E0;&#xD638; &#xADF8; chemokine &#xB098;&#xD0C0;&#xB0B4;&#xB294; &#xC950; (p &lt; &#xB610;&#xB294; = 0.04) IC MHV &#xAC10;&#xC5FC;&#xC5D0; &#xB530;&#xB77C; &#xC0DD;&#xC874;&#xC744; &#xD5A5;&#xC0C1;. &#xC640; &#xC0C1;&#xAD00; CCR1 &#xACB0;&#xD54D; &#xAC10;&#xC18C; &#xAE09;&#xC131;, &#xD558;&#xC9C0;&#xB9CC; &#xD558;&#xC9C0; &#xB9CC;&#xC131; &#xC9C8;&#xBCD1; &#xB3D9;&#xC548; CNS &#xB0B4;&#xC758; T &#xC138;&#xD3EC; &#xCD95;&#xC801; CCR1/&#xC0DD;&#xC950;&#xC5D0;&#xC11C; &#xC99D;&#xAC00; &#xC0AC;&#xB9DD;&#xB960; &#xC99D;&#xAC00; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; &#xBCF5;&#xAD6C;, CNS&#xC640; &#xC5F0;&#xACB0; &#xB418;&#xC9C0; &#xC54A;&#xC558;&#xC2B5;&#xB2C8;&#xB2E4;. T &#xC138;&#xD3EC; &#xAE09;&#xC131; &#xC9C8;&#xD658; &#xC911; CCR1/&#xC950;&#xC758; CNS&#xC5D0; &#xBC00;&#xB9E4; &#xAC10;&#xC18C;&#xC5D0;&#xB3C4; &#xBD88;&#xAD6C; &#xD558; &#xACE0; &#xAD6C;&#xC131; &#xC694;&#xC18C; &#xD638;&#xC2A4;&#xD2B8; &#xBC29;&#xC5B4;&#xC758; &#xB0A8;&#xC544; &#xBCC0;&#xACBD; &#xB418;&#xC9C0; &#xC54A;&#xC740;; T-&#xC140; effector &#xAE30;&#xB2A5; cytolytic &#xD65C;&#xB3D9;, IFN-&#xAC10;&#xB9C8; CNS &#xB0B4; &#xC2DD; &#xBC0F; &#xD655;&#xC0B0; &#xB4F1;&#xC740; CCR1 &#xC0AC;&#xC774; &#xD06C;&#xAC8C; &#xB2E4;&#xB978; + + CCR1-/-&#xC0DD;&#xC950;&#xC5D0; &#xAC10;&#xC5FC;. &#xB610;&#xD55C;, CNS&#xB85C; macrophage &#xCE68;&#xD22C;&#xB294; MHV &#xAC10;&#xC5FC; CCR1-/-&#xC0DD;&#xC950;&#xC5D0;&#xC11C; ccr1&#xC5D0; &#xBE44;&#xD574; &#xC601;&#xD5A5;&#xC744; &#xBC1B;&#xB294; + + &#xC950;. &#xB610;&#xD55C;, neuropathology&#xC758; &#xD3C9;&#xAC00; CCR1 &#xACB0;&#xD54D; &#xBC0F; &#xC57C;&#xC0DD;-&#xD0C0;&#xC785; &#xB9C8;&#xC6B0;&#xC2A4; &#xC0AC;&#xC774; demyelination &#xC2EC;&#xAC01;&#xB3C4;&#xC5D0;&#xC11C; &#xCC28;&#xC774;&#xAC00; &#xB098;&#xD0C0;&#xB0AC;&#xB2E4;. &#xD568;&#xAED8;, &#xC774;&#xB7EC;&#xD55C; &#xC5F0;&#xAD6C; &#xACB0;&#xACFC; &#xACF5;&#xAC1C; T &#xC138;&#xD3EC;&#xC640; macrophage &#xC778;&#xC2E0; &#xB9E4;&#xB9E4; ccr1&#xC5D0; &#xC758;&#xC874; &#xD558;&#xC9C0; &#xC54A;&#xC2B5;&#xB2C8;&#xB2E4;&#xACFC; &#xB9CC;&#xC131; MHV &#xAC10;&#xC5FC; &#xC2DC; &#xC0DD;&#xC874;&#xC744; &#xC2B9;&#xC9C4; &#xC2DC;&#xD0A4;&#xB294;&#xC5D0; &#xC2E0;&#xD638; ccr1&#xC5D0; &#xB300; &#xD55C; &#xC911;&#xC694; &#xD55C; &#xC5ED;&#xD560;&#xC744; &#xAC15;&#xC870;.

CCR1 &#xACB0;&#xD54D; &#xC911;&#xC559; &#xC2E0;&#xACBD; &#xC2DC;&#xC2A4;&#xD15C;&#xC758; &#xCE58;&#xBA85;&#xC801;&#xC778; &#xCF54;&#xB85C;&#xB098; &#xBC14;&#xC774;&#xB7EC;&#xC2A4; &#xAC10;&#xC5FC; &#xBBFC;&#xAC10;&#xC131;&#xC744; &#xC99D;&#xAC00; &#xC2DC;&#xD0B5;&#xB2C8;&#xB2E4;.

El papel de los receptores de quimioquinas CC 1 (CCR1) en la defensa del hu&#xE9;sped y desarrollo de la enfermedad se determin&#xF3; en un modelo de viral inducida por enfermedad neurol&#xF3;gica. Intracerebral (IC) infecci&#xF3;n de ratones con virus de la hepatitis del rat&#xF3;n (MHV) resulta en una encefalitis aguda seguida de una enfermedad cr&#xF3;nica desmielinizante similar en la patolog&#xED;a de la enfermedad esclerosis m&#xFA;ltiple (MS). No hay un aumento en la mortalidad se observ&#xF3; durante la fase aguda de la enfermedad despu&#xE9;s de la infecci&#xF3;n de ratones que carecen de MHV CCR1 (CCR1-/ -) en comparaci&#xF3;n con el tipo salvaje (CCR1 + / +) ratones. Sin embargo, 21 d&#xED;as despu&#xE9;s de la infecci&#xF3;n, el 74% de CCR1-/ - ratones hab&#xED;an sucumbido a la muerte en comparaci&#xF3;n con s&#xF3;lo el 32% de mortalidad de CCR1 ratones + / +, lo que indica que la se&#xF1;alizaci&#xF3;n a trav&#xE9;s de quimioquinas CCR1 significativamente (p &#x3C;or= 0.04) enhanced survival following IC infection with MHV. Increased mortality in CCR1-/- mice was not associated with increased viral recovery from the CNS, although CCR1 deficiency correlated with reduced T-cell accumulation within the CNS during acute, but not chronic, disease. Despite the reduction in T-cell trafficking into the CNS of CCR1-/- mice during acute disease, components of host defense remained unaltered; T-cell effector functions including cytolytic activity and proliferation and the expression of IFN-gamma within the CNS were not significantly different between CCR1+/+ and CCR1-/- infected mice. In addition, macrophage infiltration into the CNS was unaffected in MHV-infected CCR1-/- mice when compared to CCR1+/+ mice. Furthermore, assessment of neuropathology revealed no difference in the severity of demyelination between CCR1-deficient and wild-type mice. Together, these findings reveal that T-cell and macrophage trafficking are not dependent on CCR1 and highlight an important role for CCR1 signaling in promoting survival during chronic MHV infection.

Deficiencia CCR1 aumenta la susceptibilidad a la infecci&#xF3;n por coronavirus fatal del sistema nervioso central

We previously reported the cellular, functional and cytogenetic characterization of immunoresistant (IR) 13-06-IR29 and 13-06-IR30 human glioma cell clones isolated after immunoselection with alloreactive cytotoxic T lymphocytes (aCTL). Relative to the 13-06-MG parental cells, both clones resisted aCTL lysis at multiple effector to target ratios; the resistant phenotype was maintained for 13-41 cell doublings after cloning and when selective pressure was removed; cross-resistance to other inducers of apoptosis/cell death was also observed (Gomez et al, 2006; Gomez and Kruse, 2007). In this study we further characterize the IR clones for factors that may contribute to the resistance. Data obtained by in-vitro quantitative morphologic and 7-amino actinomycin D flow cytometric assays revealed reduced apoptotic cell death when IR clones were coincubated with aCTL, relative to the parental cells. Since changes in apoptosis were observed, we examined the expression patterns of apoptosis-related genes in several extracts of parental cells and IR clones using pathway-specific cDNA microarray analysis. In general, the apoptotic factors were downregulated in the IR clones. From three separate extracts analyzed separately on microarrays, three factors, ATM, caspases 3 and 8, were statistically downregulated in both IR clones. Immunoblotting of the proteins confirmed the findings. Therefore, a possible mechanism for immunoresistance in gliomas may be achieved by the downregulation of one or more genes in the apoptotic pathway.

Immunoresistant human glioma cell clones selected with alloreactive cytotoxic T lymphocytes: downregulation of multiple proapoptotic factors.

The PATZ1 gene encodes a transcription factor that belongs to the BTB/POZ group of transcriptional regulators and has been implicated as a transcriptional repressor. We cloned cDNA from glioma cell lines and found they expressed transcript variant 2 of PATZ1. We designed a specific siRNA against PATZ1 and showed that this siRNA, but not a control randomized siRNA, reduced PATZ1 expression in glioma cells as determined by quantitative PCR. In a panel of human glioma cell lines incubated with proapoptotic FasL, those transfected with PATZ1 siRNA displayed reduced cell numbers by the MTT colorimetric assay, relative to those transfected with randomized siRNA. Further studies showed that in 10-08-MG, U-251MG, U-87MG, and T98G cells PATZ1 siRNA significantly increased apoptosis in response to incubation with soluble FasL, as shown by a morphologic acridine orange/ethidium bromide apoptotic assay. Using an apoptosis specific cDNA microarray we further demonstrated that down-regulation of PATZ1 by siRNA resulted in the upregulation of death receptor pro-apoptotic genes including caspase 8 and Death Receptor 5 (DR5) in U-373MG cells. Since DR5 is the receptor for TRAIL we tested whether PATZ1 downregulation also sensitized cells to TRAIL-induced apoptosis and found that PATZ1 siRNA, but not control siRNA, sensitized U-251MG and T98G glioma cells to TRAIL-induced apoptosis. Altogether, these data demonstrate a previously unknown role for the transcription factor PATZ1 in conferring resistance to apoptosis and indicate that modulation of PATZ1 expression may be a therapeutic strategy for gliomas.

siRNA Down-regulation of the PATZ1 Gene in Human Glioma Cells Increases Their Sensitivity to Apoptotic Stimuli.

The gene for phosphatidylinositol-4-phosphate adaptor-2 (FAPP2) encodes a cytoplasmic lipid transferase with a plekstrin homology domain that has been implicated in vesicle maturation and transport from trans-Golgi to the plasma membrane. The introduction of ribozymes targeting the FAPP2 gene in colon carcinoma cells induced their apoptosis in the presence of Fas agonistic antibody. Furthermore, by quantitative PCR we showed that a siRNA specific to FAPP2, but not a randomized siRNA control, reduced FAPP2 gene expression in tumor cells. Transfection of FAPP2 siRNA into human tumor cells then incubated with FasL resulted in reduction of viable cell numbers. Also, FAPP2 siRNA transfected glioma and breast tumor cells showed significant increases in apoptosis upon incubation with soluble FasL, but the apoptosis did not necessarily correlate with increased Fas expression. These data demonstrate a previously unknown role for FAPP2 in conferring resistance to apoptosis and indicate that FAPP2 may be a target for cancer therapy.

FAPP2 gene downregulation increases tumor cell sensitivity to Fas-induced apoptosis.

Despite new additions to the standard of care therapy for high grade primary malignant brain tumors, the prognosis for patients with this disease is still poor. A small contingent of clinical researchers are focusing their efforts on testing the safety, feasibility and efficacy of experimental active and passive immunotherapy approaches for gliomas and are primarily conducting Phase I and II clinical trials. Few trials have advanced to the Phase III arena. Here we provide an overview of the cellular therapies and vaccine trials currently open for patient accrual obtained from a search of http://www.clinicaltrials.gov. The search was refined with terms that would identify the Phase I, II and III immunotherapy trials open for adult glioma patient accrual in the United States. From the list, those that are currently open for patient accrual are discussed in this review. A variety of adoptive immunotherapy trials using ex vivo activated effector cell preparations, cell-based and non-cell-based vaccines, and several combination passive and active immunotherapy approaches are discussed.

Cellular and vaccine therapeutic approaches for gliomas.

We are accruing patients to a Phase I dose escalation cellular therapy trial (www.clinicaltrials.gov, NCT01144247) involving intratumoral placement of alloreactive cytotoxic T lymphocytes (alloCTL) for recurrent gliomas. The trial is being conducted to confirm the findings of a prior pilot study that indicated this adjuvant therapy may be beneficial in extending survival of recurrent WHO grade III gliomas. To reduce costs of the cellular therapy, we tested a number of synthetic tissue culture media and found the AIM-V growth medium superior for their growth. We also moved the production of the alloCTL from artificial capillary systems to less expensive tissue culture bags. To standardize alloCTL infusates used for therapy, release criteria of ≥60% CD3+ and ≥60% viability were established that consistently translated to a 4 hr cytotoxicity of ≥30% at a 30:1 effector to target ratio. To allow time for completion of quality control testing and transport to the infusion site, we determined that 30,000 IU of human recombinant Interleukin-2 in the cellular infusates sufficiently retained cell viability and cytotoxicity to allow a 10 hr expiration time to be placed on the infusates. We identified a cytotoxic T cell subset, CD3+/CD8+/CD69+, that demonstrated upregulated IFN-γ production upon exposure to relevant target cells. The phenotypic identification of this T cell subset was indicative of robust in vitro cytotoxic function and thus will be followed to determine if it correlates with patient immune response to treatment. Finally, other therapeutic agents routinely used for glioma treatment were integrated into an analysis of alloCTL cytotoxic functionality. Temozolomide and bevacizumab do not adversely affect cytotoxic function of the alloCTL in the short-term, thus providing rationale for further investigating combinatorial chemo-immunotherapy for gliomas.

Implementing preclinical study findings to protocol design: translational studies with alloreactive CTL for gliomas.

Big potassium (BK) ion channels have several spliced variants. One spliced variant initially described within human glioma cells is the glioma BK (gBK) channel. This isoform consists of 34 aa inserted into the intracellular region of the basic BK ion channel. PCR primers specific for this inserted region confirmed that human glioma cell lines and freshly resected surgical tissues from glioblastoma multiforme patients strongly expressed gBK mRNA. Normal human brain tissue very weakly expressed this transcript. An Ab specific for this gBK isoform confirmed that human glioma cells displayed this protein in the cell membrane, mitochondria, Golgi, and endoplasmic reticulum. Within the gBK region, two putative epitopes (gBK1 and gBK2) are predicted to bind to the HLA-A*0201 molecule. HLA-A*0201-restricted human CTLs were generated in vitro using gBK peptide-pulsed dendritic cells. Both gBK1 and gBK2 peptide-specific CTLs killed HLA-A2⁺/gBK⁺ gliomas, but they failed to kill non-HLA-A2-expressing but gBK⁺ target cells in cytolytic assays. T2 cells loaded with exogenous gBK peptides, but not with the influenza M1 control peptide, were only killed by their respective CTLs. The gBK-specific CTLs also killed a variety of other HLA-A*0201⁺ cancer cells that possess gBK, as well as HLA-A2⁺ HEK cells transfected with the gBK gene. Of clinical relevance, we found that T cells derived from glioblastoma multiforme patients that were sensitized to the gBK peptide could also kill target cells expressing gBK. This study shows that peptides derived from cancer-associated ion channels maybe useful targets for T cell-mediated immunotherapy.

Glioma big potassium channel expression in human cancers and possible T cell epitopes for their immunotherapy.

Rasmussen encephalitis (RE) is a rare complex inflammatory disease, primarily seen in young children, that is characterized by severe partial seizures and brain atrophy. Surgery is currently the only effective treatment option. To identify genes specifically associated with the immunopathology in RE, RNA transcripts of genes involved in inflammation and autoimmunity were measured in brain tissue from RE surgeries and compared with those in surgical specimens of cortical dysplasia (CD), a major cause of intractable pediatric epilepsy.

Differential expression of interferon-γ and chemokine genes distinguishes Rasmussen encephalitis from cortical dysplasia and provides evidence for an early Th1 immune response.

Individual or combined strategies of cellular therapy with alloreactive CTLs (alloCTL) and gene therapy using retroviral replicating vectors (RRV) encoding a suicide prodrug activating gene were explored for the treatment of breast tumors metastatic to the brain.

Combined alloreactive CTL cellular therapy with prodrug activator gene therapy in a model of breast cancer metastatic to the brain.

New treatments are needed for brain metastasis, which is associated with high morbidity and mortality. Two novel cellular and gene therapy modalities were evaluated in xenograft models for human breast cancer. The individual and especially the combined treatments with alloreactive cytotoxic T lymphocytes and replicating retroviral vectors coding for prodrug activating enzymes followed later with nontoxic prodrug demonstrated efficacy without off-target effects.

Combining cellular and gene therapy approaches for treatment of intracranial tumors.

Big Potassium (BK) ion channels have several splice variants. One splice variant initially described within human glioma cells is called the glioma BK channel (gBK). Using a gBK-specific antibody, we detected gBK within three human small cell lung cancer (SCLC) lines. Electrophysiology revealed that functional membrane channels were found on the SCLC cells. Prolonged exposure to BK channel activators caused the SCLC cells to swell within 20 minutes and resulted in their death within five hours. Transduction of BK-negative HEK cells with gBK produced functional gBK channels. Quantitative RT-PCR analysis using primers specific for gBK, but not with a lung-specific marker, Sox11, confirmed that advanced, late-stage human SCLC tissues strongly expressed gBK mRNA. Normal human lung tissue and early, lower stage SCLC resected tissues very weakly expressed this transcript. Immunofluorescence using the anti-gBK antibody confirmed that SCLC cells taken at the time of the autopsy intensely displayed this protein. gBK may represent a late-stage marker for SCLC. HLA-A*0201 restricted human CTL were generated in vitro using gBK peptide pulsed dendritic cells. The exposure of SCLC cells to interferon-γ (IFN-γ) increased the expression of HLA; these treated cells were killed by the CTL better than non-IFN-γ treated cells even though the IFN-γ treated SCLC cells displayed diminished gBK protein expression. Prolonged incubation with recombinant IFN-γ slowed the in vitro growth and prevented transmigration of the SCLC cells, suggesting IFN-γ might inhibit tumor growth in vivo. Immunotherapy targeting gBK might impede advancement to the terminal stage of SCLC via two pathways.

Article	Year
Antibody targeting of the CC chemokine ligand 5 results in diminished leukocyte infiltration into the central nervous system and reduced neurologic disease in a viral model of multiple scler... Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 15034013	2004
Therapeutic neutralization of CXCL10 decreases secondary degeneration and functional deficit after spinal cord injury in mice. Regenerative medicine\| PubMed ID: 17907930	2007
CCR1 deficiency increases susceptibility to fatal coronavirus infection of the central nervous system. Viral immunology\| PubMed ID: 18158733	2007
Immunoresistant human glioma cell clones selected with alloreactive cytotoxic T lymphocytes: downregulation of multiple proapoptotic factors. Gene therapy & molecular biology\| PubMed ID: 19066635	2008
siRNA Down-regulation of the PATZ1 Gene in Human Glioma Cells Increases Their Sensitivity to Apoptotic Stimuli. Cancer therapy\| PubMed ID: 19081762	2008
FAPP2 gene downregulation increases tumor cell sensitivity to Fas-induced apoptosis. Biochemical and biophysical research communications\| PubMed ID: 19341712	2009
Cellular and vaccine therapeutic approaches for gliomas. Journal of translational medicine\| PubMed ID: 20946667	2010
Implementing preclinical study findings to protocol design: translational studies with alloreactive CTL for gliomas. American journal of translational research\| PubMed ID: 22347526	2012
Glioma big potassium channel expression in human cancers and possible T cell epitopes for their immunotherapy. Journal of immunology (Baltimore, Md. : 1950)\| PubMed ID: 22844111	2012
Differential expression of interferon-γ and chemokine genes distinguishes Rasmussen encephalitis from cortical dysplasia and provides evidence for an early Th1 immune response. Journal of neuroinflammation\| PubMed ID: 23639073	2013
Combined alloreactive CTL cellular therapy with prodrug activator gene therapy in a model of breast cancer metastatic to the brain. Clinical cancer research : an official journal of the American Association for Cancer Research\| PubMed ID: 23780889	2013
Combining cellular and gene therapy approaches for treatment of intracranial tumors. Oncoimmunology\| PubMed ID: 24244896	2013
Small cell lung cancer cells express the late stage gBK tumor antigen: a possible immunotarget for the terminal disease. American journal of translational research\| PubMed ID: 24936214	2014

Michelle J. Hickey

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