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.