TARGETING THE B7 CD28-CTLA-4 COSTIMULATORY SYSTEM IN CNS AUTOIMMUNE-DISEASE/

The B7/CD28:CTLA-4 costimulatory pathway plays a critical role in dete rmining the fate of immmune responses (activation vs. down-regulation) and is a highly promising therapeutic target for treating autoimmune diseases. In this review, we highlight the mechanisms by which this co stimulatory pathway operates emphasizing the role of the different com ponents in the pathogenesis of relapsing experimental autoimmmune ence phalomyelitis, a CD4 T cell-mediated autoimmune model of multiple scle rosis. The separate and distinct roles of B7-1, B7-2 and CTLA-4 in pos itive and negative regulation of autoimmune pathogenesis are considere d and a working model is proposed. (C) 1998 Elsevier Science B.V. All rights reserved.