Regulatory T Cells Control Autoimmunity In Vivo by Inducing Apoptotic Depletion of Activated Pathogenic Lymphocytes

摘要

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 beta8.2 chain-derived peptidesin the context of MHC. How this regulation affects the face of target Vbeta8.2~+ T lymphocytes in vivo that mediate experimental autoimmune encephalomyelitis has remained unknown. The present study using immunoscope and CFSE-labeing 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 Vbeta8.2~+ T cells, but not subdominant Vbeta13~+ T cell repertoire and at the same time results in protection from disease. These studies are the first in clearly elucidating the face of myelin basic protein-specific encephalitogenic T cells in vivo following regulation.