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More MS news articles for July 2003

Regulatory CD8+ T cells fine-tune the myelin basic protein-reactive T cell receptor V{beta} repertoire during experimental autoimmune encephalomyelitis

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12824465&dopt=Abstract

Proc Natl Acad Sci U S A. 2003 Jun 24
Jiang H, Curran S, Ruiz-Vazquez E, Liang B, Winchester R, Chess L.
College of Physicians and Surgeons, Columbia University, New York, NY 10032.

A significant number of self-reactive T cell clones escape thymic negative selection and are released into the periphery, where some are potentially pathogenic.

The clonal expansion of self-reactive T cells is known to be limited during initial antigen encounter by apoptotic or anergic mechanisms, regulatory CD4(+) T cells, and cytokines.

Here we report that superimposed on these mechanisms, during the evolution of autoimmunity in experimental autoimmune encephalomyelitis (EAE), CD8(+) T cells are induced, which fine-tune the peripheral self-reactive T cell receptor (TCR) repertoire.

We assayed the myelin basic protein-reactive TCR repertoire in naive, EAE-recovered mice as well as EAE-recovered mice depleted of CD8(+) T cells by TCRVbeta surface expression, complementarity-determining region 3 length distribution, and complementarity-determining region 3 sequencing analysis.

In EAE-recovered mice, certain myelin basic protein-reactive CD4(+)Vbeta8.2(+) clones are significantly decreased and this decrease is not observed if CD8(+) T cells were depleted from these mice.

The clones that persist in CD8(+) T cell-intact mice are highly diverse in contrast to the clones expanded in CD8(+) T cell-depleted mice, which are dominated by the significant outgrowth of a few clones.

Importantly, the T cell clones that expand in the absence of CD8(+) T cell control are enriched in potentially pathogenic self-reactive T cell clones capable of inducing EAE in vivo.