[T cell tolerance and autoimmune disease]

T cell tolerance is ensured by several complementary mechanisms arranged in a fail-safe manner, which contain clonal deletion in the thymus, and clonal anergy, activation-induced cell death, and suppression in the periphery. What is still unclear is the conditions under which, and the mechanisms by which, all these T cell tolerance systems can break down, inducing autoimmune phenomenon and then autoimmune disease. Fas or FasL mutant and CTLA-4 knock-out mice have successfully unraveled the molecular mechanisms for breakdown and maintenance of some T cell tolerance. Although they are of great theoretical interest, their involvement in the pathogenesis of the major autoimmune diseases remains controversial. In this minireview discussed are their precise mechanisms and possible importance in therapeutic immune intervention.