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

H Jiang, S Curran, E Ruiz-Vazquez… - Proceedings of the …, 2003 - National Acad Sciences
H Jiang, S Curran, E Ruiz-Vazquez, B Liang, R Winchester, L Chess
Proceedings of the National Academy of Sciences, 2003National Acad Sciences
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 …
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 TCRVβ 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+Vβ8.2+ 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.
National Acad Sciences