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Nat Immunol. 2003 Apr;4(4):350-4. Epub 2003 Mar 3.

Aire regulates negative selection of organ-specific T cells.

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ACRF Genetics Lab, Medical Genome Centre, John Curtin School of Medical Research, The Australian National University, ACT 2601 Australia.


Autoimmune polyendocrinopathy syndrome type 1 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 1 is caused by failure of a specialized mechanism for deleting forbidden T cell clones, establishing a central role for this tolerance mechanism.

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