Liston, AdrianLesage, SylvieWilson, JudithPeltonen, LGoodnow, Christopher2015-12-131529-2908http://hdl.handle.net/1885/89727Autoimmune polyendocrinopathy syndrome type I is a recessive Mendelian disorder resulting from mutations in a novel gene, AIRE, and is characterized by a spectrum of organ-specific autoimmune diseases. It is not known what tolerance mechanisms are defective as a result of AIRE mutation. By tracing the fate of autoreactive CD4+ T cells with high affinity for a pancreatic antigen in transgenic mice with an Aire mutation, we show here that Aire deficiency causes almost complete failure to delete the organ-specific cells in the thymus.These results indicate that autoimmune polyendocrinopathy syndrome I is caused by failure of a specialized mechanism for deleting forbidden T cell clones, establishing a central role for this tolerance mechanism.Keywords: autoimmune regulator protein; CD4 antigen; cell antigen; transcription factor; unclassified drug; animal cell; animal experiment; animal model; antibody specificity; article; autoimmune disease; autoimmune polyendocrinopathy candidiasis ectodermal dystrop200310.1038/ni9062015-12-12