Intrathymic T-cell ontogeny: Crossroad between immune competence and tolerance.

The weak balance between immune competence and immune tolerance is reflected in the coexistence, in the same inborn error of immunity, of susceptibility to infections and predisposition to develop immune dysregulatory features. Different mechanisms are implicated in the pathogenesis of immunodeficiency and autoimmunity. The thymus plays a crucial role in the development of both immune tolerance and immune competence. Alterations of thymus development and function may lead to inborn errors of immunity presenting with a wide spectrum of dysregulation of the immune system ranging from severely deficient T-cell function, as in severe combined immunodeficiency, to severely dysregulated T-cell function, as in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. The extreme expression of the dysregulation of the immune system in thymus defects is embodied by phenocopies in which autoantibodies produced as a result of the immune dysregulation are themselves responsible for the immune defect.