Figure1. Left panel: Modified from Autoimmune Polyglandular Syndromes in Pediatric Endocrinology 4th Edition, Ed. Sperling MA. (with permission of the authors Drs. Michael Haller, William Winter, Desmond Schatz). A developing T-cell migrates from its origins in the bone marrow to the thymus where it matures and acquires its repertoire of receptors. The expression of self-antigens, including ectopic expression of antigens mediated via the AIRE gene, results in apoptosis of the T-cell possessing the complementary receptor, and prevention of the T-cell entering the periphery, a fate of almost all T-cells. A small fraction of T-cells enter the periphery where they remain anergic to self-antigens, but can mount an immune response to non-self-antigens. Right panel: Failure of self-tolerance, due to non-expression of self-antigens as would occur with inactivating mutations of the AIRE gene, results in failure of central tolerance as well as failure of recognition of self-antigens that leads to an auto-immune response.