Control of Autoimmunity by Regulatory T Cells

The development of autoimmune disease involves a breakdown in the mechanisms that control self vs non-self discrimimation. The primary mechanism that leads to self tolerance is thymic deletion of autoreactive T cells, but thymic deletion is not perfect and autoreactive T cells do escape to the periphery. Cells that escape thymic deletion are then subject to mechanisms of peripheral tolerance including the induction of anergy t as well as T cell ignorance/indifference of the recognition of autoantigens. However, anergy can be reversed and ignorant T cell populations have the potential to be activated when their target self-antigens are released into the lymphoid system during the course of an infectious insult or when activated by cross-reactive antigens present on infectious agents. Passive mechanisms for the induction of self tolerance may therefore be insufficient to control the activation of autoreactive T cells. Evidence has recently been obtained for an active mechanism of immune suppression in which a distinct subset of T cells suppresses the activation of autoreactive T cells that have escaped the other mechanisms of tolerance induction. Two experimental models have been developed which have allowed the definition of unique populations of regulatory T cells. In one model, autoimmunity is induced by depletion of regulatory T cells from adult animals, while in the second model, the development of regulatory T cells is abolished in neonatal animals.