Central Tolerance of T Cells

The immune system is constructed to tolerate self antigens but give vigorous responses to foreign antigens. How this state of self/nonself discrimination is maintained is controversial. In the case of T cells, many self antigens are transported to the thymus via the bloodstream and induce tolerance (clonal deletion) of self-reactive thymocytes in situ. Although such central tolerance in the thymus is well documented, it is often argued that full induction of tolerance requires peripheral mechanisms such as suppression or induction of anergy. This article proposes that steady-state tolerance of T cells to self components is due solely to central tolerance to circulating self antigens combined with sequestration of tissue-specific antigens. Backup mechanisms for tolerance do exist but such immunoregulation only operates when self tolerance breaks. This scheme allows the immune system to give unrestricted primary responses to foreign antigens.