THE CD28-B7 COSTIMULATORY PATHWAY AND ITS ROLE IN AUTOIMMUNE-DISEASE

The activation of naive CD4+ T cells requires two discrete signals: a signal delivered by the T cell receptor following recognition of antig en and an accessory signal transduced when costimulatory receptors int eract with their ligands. Particularly important in the development of an immune response to foreign antigens is the T cell molecule CD28, w hich delivers a potent costimulus when engaged by ligands, B7-1 and B7 -2, on antigen-presenting cells. It is interesting that blockade of B7 molecules, which disrupts interactions with CD28 and prevents deliver y of the CD28 costimulus, also alters the immune responses to self ant igens and prevents the development of clinical disease in murine model s of systemic and organ-specific autoimunity. Herein we review the rol es of CD28 and its B7 ligands in the pathogenesis of autoimmunity, dis cuss efforts to treat animal models of autoimmunity by modifying the C D28 signal, and consider the mechanisms by which manipulation of the C D28 signal alters the course of experimental autoimmune disease.