CTLA4 gene polymorphism and autoimmunity

CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA4) are two receptors that have critical but opposing functions in T-cell stimulation. CD28 promotes a number of T-cell activities, whereas in contrast CTLA4 is an essential inhibitor of T-cell responses. Because of its inhibitory role, CTLA4 is a strong candidate susceptibility gene in autoimmunity and several studies suggest disease-associated polymorphisms. In this review, we discuss recent progress in relating CTLA4 polymorphisms to disease susceptibility and consider the putative mechanisms by which CTLA4 may act to inhibit autoimmunity.