Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes.
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.
Madakamutil
Loui Thomas
LT
Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121, USA.
Maricic
Igor
I
Sercarz
Eli
E
Kumar
Vipin
V
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology*; D005260:Female; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008213:Lymphocyte Activation; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000008:administration & dosage / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology*; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology
D004676:Myelin Basic Protein; D010446:Peptide Fragments; D016693:Receptors, Antigen, T-Cell, alpha-beta; C074815:myelin basic protein 1-9