Extrathymic mechanisms of T cell tolerance: Lessons from autoimmune gastritis

While the thymus plays a key role in the prevention of many autoimmune phenomena it is clear that robust mechanisms external to the thymus are also vital in controlling self-reactive T cells. Here we review the current concepts in the field of extrathymic tolerance and use recent studies of autoimmune gastritis to illustrate how T cells directed to a prominent, clinically relevant autoantigen, namely the gastric proton pump, can be silenced with little or no thymic involvement. Autoimmune gastritis represents one of the most thoroughly characterised autoimmune systems and the knowledge and tools available to study this disease will continue to allow a thorough assessment of the genetic, cellular and molecular events that underlie tolerance and autoimmunity.