T-cell activation in autoimmune and inflammatory diseases

Recent progress in experimental models and human genetic linkage studies have provided new insight into the pathogenesis of autoimmunity. Both antigen-specific and antigen-nonspecific signals are crucial in the development of autoimmune disease. Interestingly, several of the single gene loci that have been identified as potential causes of autoimmune disease encode molecules that regulate antigen-nonspecific modulation of immunity. The focus of this review is the role of the opposing signals transduced by the CD28 and cytotoxic T-lymphocyte antigen-4 receptors that bind the B7 costimulatory ligands. Recent studies suggest that CD28 signals activate T cells, whereas cytotoxic T-lymphocyte antigen-4 signals deactivate T cells. importantly, both signals contribute to the induction of autoimmunity and offer novel targets for future therapeutic strategies to treat autoimmune disease.