Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes |
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Authors: | Madakamutil Loui Thomas Maricic Igor Sercarz Eli Kumar Vipin |
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Affiliation: | Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA. |
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Abstract: | Clinical autoimmunity requires both activation of self-reactive T cells as well as a failure of peripheral tolerance mechanisms. We previously identified one such mechanism that involves regulatory T cells recognizing TCR V beta 8.2 chain-derived peptides in the context of MHC. How this regulation affects the fate of target V beta 8.2(+) T lymphocytes in vivo that mediate experimental autoimmune encephalomyelitis has remained unknown. The present study using immunoscope and CFSE-labeling analysis demonstrates that the expansion of regulatory CD4 and CD8 T cells in vivo results in apoptotic depletion of the dominant, myelin basic protein-reactive V beta 8.2(+) T cells, but not subdominant V beta 13(+) T cells. The elimination of only activated T cells by this negative feedback mechanism preserves the remainder of the naive V beta 8.2(+) T cell repertoire and at the same time results in protection from disease. These studies are the first in clearly elucidating the fate of myelin basic protein-specific encephalitogenic T cells in vivo following regulation. |
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