simultaneous-quantification-t-cell-receptor-excision-circles-trecs-k

Simultaneous Quantification of T-Cell Receptor Excision Circles (TRECs) and K-Deleting Recombination Excision Circles (KRECs) by Real-time PCR

T-cell receptor excision circles (TRECs) and K-deleting recombination excision circles (KRECs) are circularized DNA elements formed during recombination ...

Spedali Civili di Brescia

Like the immunoglobulin genes, the T-cell receptor genes are generated by rearrangements of non-contiguous genomic V, D and J regions, but unlike the immunoglobulin genes, somatic hypermutation is an infrequent event in T-cell receptor genes. Here, we describe the occurrence of spontaneous mutations in the constant regions of the T-cell receptor beta chains of T lymphocytes obtained from two babies who underwent in utero transplantation because of severe combined immunodeficiency. In view of the fact that in babies receiving transplants before birth, hematopoietic chimerism is consistently present, the lymphocytes are likely to be under chronic activation, which may represent a relevant biologic stimulus for generating the observed T-cell receptor hypermutation. This possibility is supported by the finding that the highest number of mutations was identified in clonally expanded T cells. These results provide further support indicating that hypermutation of the T-cell receptor genes may indeed occur, given the necessary conditions.

Mutations of the T-cell receptor constant region after in utero stem cell transplantation.

Reduced CD4+ lymphocytes have been recently found in peripheral blood of children with active opsoclonus-myoclonus syndrome. The authors identified 2 children who recovered from this syndrome, one of whom showed reduced CD4+ lymphocytes 2 years after the disease onset. Except for a decrease of "naive" CD45RA+ CD4+ population and a mild restriction of T-cell heterogeneity in this patient, probably related to the immune response to viral infections, no alterations of T-cell homeostasis and function were found in either child. Therefore, the decrease of CD4+ cells may persist after clinical recovery, but the causes of this abnormality cannot be ascribed to intrinsic T-cell defects.

T-lymphocyte production, function, and death in children who recovered from opsoclonus-myoclonus syndrome.

We developed a real-time PCR assay to simultaneously measure the mRNA level of type I interferon (IFN) receptor (IFNAR) components in peripheral blood cells of children with chronic immune stimulation due to HIV infection. All patients were undergoing antiretroviral therapy and were divided into two groups on the basis of the induction of MxA mRNA, a marker of type I IFN bioactivity. We found that IFNAR-2 subunit mRNA was higher than that of the IFNAR-1 subunit, that the mRNA for the IFNAR-2.2 functional isoform was more expressed than that for the truncated IFNAR-2.1 isoform, and both were much more represented than that of the IFNAR-2.3 soluble isoform. We also demonstrated that soluble isoform mRNA was significantly diminished in the subgroup of patients with MxA mRNA below the cutoff value (determined as the 99th percentile of MxA measured in healthy controls). These results suggest that downregulation of the soluble receptor isoform, which would not compete with the functional isoform for binding to the target cytokine, would give type I IFN, eventually induced in these patients in the case of viral reactivation, the opportunity to promptly exert its antiviral activity.

Decreased type I interferon receptor-soluble isoform in antiretroviral-treated HIV-positive children.

Reports differ on the association between epilepsy and celiac disease, an immune-mediated enteropathy triggered by the ingestion of gluten in genetically susceptible individuals. In this study, 272 Italian children with epilepsy and 300 healthy children were screened for anti-gliadin and anti-transglutaminase immunoglobulin A and G; positive and borderline samples were tested for the presence of anti-endomysium antibodies. The prevalence of antibodies related to celiac disease was comparable to that of healthy controls. In keeping with this observation, Italian epileptic children should not be considered a group at risk for celiac disease.

Article	Year
Mutations of the T-cell receptor constant region after in utero stem cell transplantation. Immunogenetics\| PubMed ID: 15138733	2004
T-lymphocyte production, function, and death in children who recovered from opsoclonus-myoclonus syndrome. Pediatric hematology and oncology\| PubMed ID: 17130111	2007
Decreased type I interferon receptor-soluble isoform in antiretroviral-treated HIV-positive children. Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research\| PubMed ID: 18338950	2008
Celiac disease-related antibodies in Italian children with epilepsy. Pediatric neurology\| PubMed ID: 19520271	2009

Monica Valotti

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