Normal thymic architecture and negative selection are associated with Aireexpression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)

T cell development is tightly controlled by thymic stromal cells. Alteratio ns in stromal architecture affect T cell maturation and the development of self-tolerance. The monogenic autoimmune syndrome APECED (autoimmune-polyen docrinopathy-candidiasis-ectodermal dystrophy) is characterized by the loss of self-tolerance to multiple organs. Although mutations in the autoimmune regulator (AIRE) gene are responsible for this disease, the function of AI RE is not known. Here we report on the spatial and temporal pattern of muri ne Aire expression during thymic ontogeny and T cell selection. Early durin g development, thymic Aire transcription is critically dependent on ReIB an d occurs in epithelial cells in response to lymphocyte-mediated signals. In adult tissue, Aire expression is confined to the medulla and the corticome dullary junction, where it is modulated by thymocytes undergoing negative s election. Aire may determine thymic stromal organization and with it the in duction of self-tolerance.