T cell deletion in high antigen dose therapy of autoimmune encephalomyelitis.
Encounters with antigen can stimulate T cells to become activated and proliferate, become nonresponsive to antigen, or to die. T cell death was shown to be a physiological response to interleukin-2-stimulated cell cycling and T cell receptor reengagement at high antigen doses. This feedback regulatory mechanism attenuates the immune response by deleting a portion of newly dividing, antigen-reactive T cells. This mechanism deleted autoreactive T cells and abrogated the clinical and pathological signs of autoimmune encephalomyelitis in mice after repetitive administration of myelin basic protein.
Critchfield
J M
JM
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.
Racke
M K
MK
Zúñiga-Pflücker
J C
JC
Cannella
B
B
Raine
C S
CS
Goverman
J
J
Lenardo
M J
MJ
D000818:Animals; D000941:Antigens / Q000276:immunology*; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002455:Cell Division; D002478:Cells, Cultured; D003574:Cytochrome c Group / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D007108:Immune Tolerance; D007167:Immunotherapy; D007376:Interleukin-2 / Q000276:immunology / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology; D009186:Myelin Sheath / Q000276:immunology / Q000473:pathology; D013116:Spinal Cord / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D000941:Antigens; D003574:Cytochrome c Group; D007376:Interleukin-2; D004676:Myelin Basic Protein