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In JoVE (1)
Other Publications (5)
Articles by Harley Y. Tse in JoVE
JoVE Immunology and Infection
Overcoming Unresponsiveness in Experimental Autoimmune Encephalomyelitis (EAE) Resistant Mouse Strains by Adoptive Transfer and Antigenic Challenge
1Department of Medicine, Section of Cardiology, St. John-Providence Health System, 2Department of Immunology and Microbiology, Wayne State University School of Medicine
Certain mouse strains are able to resist induction of experimental autoimmune encephalomyelitis (EAE) with myelin basic protein. Described here is a simple immunization protocol that reverses the unresponsiveness and induces paralytic disease in several typical EAE resistant mouse stains.
Other articles by Harley Y. Tse on PubMed
Distinct Immune Regulation of the Response to H-2b Restricted Epitope of MOG Causes Relapsing-remitting EAE in H-2b/s Mice
To find immune mechanisms underlying relapse regulation, we developed a model of relapsing-remitting experimental autoimmune encephalomyelitis (EAE) in (B6xSJL) F1 (H-2(b/s)) mice by immunization with myelin oligodendrocyte glycoprotein peptide 35-55 (MOG(35-55)) and compared with low/non-relapsing B6 (H-2(b)) mice. In relapsing H-2(b/s) mice, inflammatory lesions scattered throughout the white matter with extensive demyelination, consisted of CD4(+) T and B220(+) B cells with fewer Mac3(+) macrophages. Memory T cell proliferation to MOG(35-55) was significantly enhanced. Switch of macrophage chemoattractant protein-1 (MCP-1) production from GFAP(+) astrocytes to CD3(+) T cells was observed. Distinct patterns of inflammation and demyelination, MOG(35-55) memory T cell response and regulation of MCP-1 are associated with relapsing H-2(b/s) phenotype.
Adoptive Transfer of Myelin Basic Protein-induced Experimental Autoimmune Encephalomyelitis Between SJL and B10.S Mice: Correlation of Priming Milieus with Susceptibility and Resistance Phenotypes
To study the mechanisms of EAE resistance, we directly transfer MBP-primed EAE-susceptible SJL lymph node cells into EAE-resistant B10.S recipients and vice versa. These transfers were unsuccessful because of strong alloreactivity between the two strains. Neonatal tolerance to SJL antigens was induced in B10.S mice and in these hosts MBP-primed SJL lymph node cells readily induce development of adoptive EAE. Conversely, transfer of MBP-primed B10.S lymph node cells into EAE-susceptible (SJL x B10.S)F1 recipients failed to induce EAE. These results are consistent with the notion that the priming milieus in the donor mice affect the expression of susceptible and resistant phenotypes.
High Cell Surface Expression of CD4 Allows Distinction of CD4(+)CD25(+) Antigen-specific Effector T Cells from CD4(+)CD25(+) Regulatory T Cells in Murine Experimental Autoimmune Encephalomyelitis
Analysis of T regulatory cells (Treg) and T effector cells (Teff) in experimental autoimmune encephalomyelitis is complicated by the fact that both cell types express CD4 and CD25. We demonstrate that encephalitogenic T cells, following antigen recognition, up-regulate cell surface expression of CD4. The CD4(high) sub-population contains all of the antigen response as shown by proliferation and cytokine secretion, and only these cells are capable of transferring EAE to naive animals. On the other hand, a FACS separable CD25(+) sub-population of cells displayed consistent levels of CD4 prior to and after antigen stimulation. These cells displayed characteristics of Treg, such as expressing high levels of the Foxp3 gene and the ability to suppress mitogenic T cell responses.
T Cells That Trigger Acute Experimental Autoimmune Encephalomyelitis Also Mediate Subsequent Disease Relapses and Predominantly Produce IL-17
Earlier studies showed that donor T cells that initiated a murine adoptive EAE persisted in the CNS of the recipients throughout the subsequent relapsing cycles. To clarify the functions of the persistent donor T cells in EAE relapsing disease, anti-Thy-1 antibodies were used to deplete these cells. Results showed that such treatment abrogated subsequent relapsing cycles in these animals. In addition, it was evident that a shift in cytokine profile occurred during acute and relapsing disease phases. These results unambiguously support the appropriateness of targeting T cells with specificity for the priming antigen in design of therapeutic approaches for MS.
Differential Levels of Resistance to Disease Induction and Development of Relapsing Experimental Autoimmune Encephalomyelitis in Two H-2b-restricted Mouse Strains
Besides the major histocompatibility complex (MHC) genes, background genes are believed to influence the encephalitogenicity of SJL(H-2(s)) and B10.S (H-2(s)) mice responding to myelin basic protein (MBP). A new mouse strain was constructed to study the effects of the SJL genetic background in mice responding to H-2(b)-restricted neuroantigens. Although the SJL.B (H-2(b)) mouse remained resistant to MBP in active EAE induction, the disease severity was uniformly higher in MOG-induced active EAE and in MBP-induced adoptive EAE when compared to those of B6 (H-2(b)) mice. Treatment of mice with anti-CD25 antibodies prior to immunization caused 60% of SJL.B mice to become susceptible to MBP-induced EAE while only 14% of B6 mice were converted. In addition, MOG-induced EAE in SJL.B mice followed a remitting-relapsing disease course while B6 mice only exhibited monophasic or chronic episodes. The new SJL.B mouse strain provides a valuable tool for studying EAE resistance and remitting-relapsing disease in H-2(b) mice.
