In Situ Tolerance within the Central Nervous System as a Mechanism for Preventing Autoimmunity

Brabb, Thea; von Dassow, Peter; Ordonez, Nadia; Schnabel, Bryan; Duke, Blythe; Goverman, Joan

Activation of self-reactive T cells is one of the first steps in the development of autoimmune disease. The pool of autoreactive T cells available for activation is limited to a large extent by mechanisms of tolerance induction that eliminate self-reactive T cells (1) . Animal models of autoimmune disease, however, demonstrate that some self-reactive T cells remain in the periphery. These T cells are described as "ignorant" because they do not cause autoimmune disease when encountering self-antigen in vivo unless the self-antigen is presented in an immunostimulatory context (2, 3) . Experimental allergic encephalomyelitis (EAE), 1 an animal model of multiple sclerosis (MS), illustrates this phenomenon. EAE is induced by immunization with central nervous system (CNS) antigens such as myelin basic protein (MBP) in CFA (4) . Recognition of MBP in this context activates naive T cells circulating in the periphery, which then enter the CNS and initiate destruction of myelin (5) . In the absence of experimental intervention, the MBP-specific T cells are not activated and do not induce EAE.