Schematic illustration of thymic and peripheral events in APECED. Tissue-restricted antigen-specific T cells are not deleted in APECED thymus because of the deficient function of AIRE in medullary thymic epithelial cells (mTEC), and escape to cause tissue damage in endocrine organs in APECED patients. We speculate that, because of aberrant cell death or alternative danger signal, human AIRE-deficient thymus (and thymomas) assume some functions of secondary lymphoid organs, with associated overproduction of type I IFNs by thymic DCs. These DCs are activated and present a broad spectrum of type I interferons to autoimmunize specific T and then B cells. The resulting high titer neutralizing antibodies inhibit ISG responses of PBMCs to basal circulating levels of type I IFNs. Autoreactive T cells infiltrating target endocrine tissues secrete IFN-γ. This induces the production of CXCL10 and further expansion of the adjacent infiltrates.