In AIRE deficiency, self-reactive CD4+ T lymphocytes escape from the thymus into the periphery and are both necessary and sufficient to cause autoimmune tissue infiltration and destruction, as shown by adoptive transfer experiments of Aire−/− CD4+ T lymphocytes in immunodeficient mice, by CD4+ T lymphocyte depletion experiments in Aire−/− mice, and by experiments in Aire−/−Tcra−/− mice (3, 4, 41, 42). Here, CD4 is linked to hyperinsulinemic hypoglycemia, familial, 4.