MHC Class-II-Restricted Antigen Presentation by Myelin Basic Protein-Specific CD4+ T Cells Causes Prolonged Desensitization and Outgrowth of CD4− Responders

• Published in: Cellular immunology 2001-08, Vol.212 (1), p.51-62
• Main Authors: Mannie, Mark D., Norris, Marcus S.
• Format: Article
• Language: English
• Subjects: Animals; Antigen Presentation; Autoimmunity; CD4 Antigens - immunology; CD4-Positive T-Lymphocytes - immunology; Encephalomyelitis, Autoimmune, Experimental - immunology; experimental autoimmune encephalomyelitis (EAE); Histocompatibility Antigens Class II - immunology; multiple sclerosis (MS); Multiple Sclerosis - immunology; Myelin Basic Protein - immunology; Rats; T cell antigen receptors; T helper cells; tolerance
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.2001.1843

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.