Age-dependent T cell tolerance and autoimmunity to myelin basic protein

Experimental autoimmune encephalomyelitis (EAE), an animal model for multip le sclerosis, is induced by activating a subset of myelin basic protein (MB P)-specific T cells that have escaped tolerance induction. Here, we define the tolerance mechanisms that eliminate the majority of MBP-specific T cell s from the periphery. We show that MBP-specific T cells undergo central tol erance mediated by bone marrow-derived antigen-presenting cells presenting exogenously derived MBP epitopes. The efficiency of tolerance is age depend ent, reflecting the developmentally regulated expression of MBP. Dependence of tolerance on the amount of MBP expressed in vivo results in an age wind ow of susceptibility to EAE in mice that peaks during puberty. These result s suggest that facto rs regulating expression of self-antigens in vivo can influence susceptibility to autoimmunity.