MHC class-II-restricted antigen presentation by myelin basic protein-specific CD4+ T cells causes prolonged desensitization and outgrowth of CD4- responders.
T cells express MHC class II glycoproteins under various conditions of activation or inflammation. To assess whether T cell APC (T-APC) activity had long-term tolerogenic consequences, myelin basic protein (MBP)-specific rat T cells were induced to acquire MBP-derived I-A complexes to promote reciprocal antigen presentation. T-T antigen presentation caused extensive cell death among T-APC and MBP-specific T responders and caused long-term desensitization of surviving responders. Addition of the anti-I-A mAb OX6 to activated I-A+ responders inhibited T-APC activity, accelerated recovery from postactivation refractoriness, and prevented long-term loss of reactivity in responder T cells. Antigenic activation of responder T cells with irradiated T-APC induced profound losses in reactivity that lasted for over 1 month of propagation in IL-2 and was associated with preferential outgrowth of CD4- T cells. Antigen-activated CD4- T cells exhibited more rapid IL-2-dependent growth that eventually normalized compared to CD4+ T cells 1-2 months after antigen exposure. In conclusion, expression of T-APC activity by activated T cells represents an important negative feedback pathway that depletes antigen-reactive T cells and causes long-term desensitization of surviving T cells. Hence, T cell APC may be an important mechanism of self-tolerance.
Mannie
M D
MD
Department of Microbiology and Immunology, Brody Medical Sciences Building, East Carolina University School of Medicine, Greenville, NC 27858-4354, USA. manniem@mail.ecu.edu
Norris
M S
MS
D000818:Animals; D017951:Antigen Presentation; D015551:Autoimmunity; D015704:CD4 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D009103:Multiple Sclerosis / Q000276:immunology; D004676:Myelin Basic Protein / Q000276:immunology*; D051381:Rats
D015704:CD4 Antigens; D000949:Histocompatibility Antigens Class II; D004676:Myelin Basic Protein