Regulatory CD 8 T cells fine-tune the myelin basic protein-reactive T cell receptor V repertoire during experimental autoimmune encephalomyelitis

Content Provider	Semantic Scholar
Author	Jiang Curran, Stephanie E. Ruiz-Vázquez, E. Liang, Bitao Winchester, R. Chess, Leonard
Copyright Year	2003
Abstract	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 TCRV 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 V 8.2 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.
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Alternate Webpage(s)	http://www.pnas.org/content/100/14/8378.full.pdf
Language	English
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Content Type	Text
Resource Type	Article