Aire regulates negative selection of organ-specific T cells

Nat Immunol. 2003 Apr;4(4):350-4. doi: 10.1038/ni906. Epub 2003 Mar 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / genetics
  • Autoantigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Clonal Deletion / genetics*
  • Clonal Deletion / immunology
  • Mice
  • Mice, Transgenic
  • Organ Specificity / immunology
  • Pancreas / immunology
  • Polyendocrinopathies, Autoimmune / genetics*
  • Receptors, Interleukin-2 / metabolism
  • Thymus Gland / immunology
  • Transcription Factors / genetics*


  • APECED protein
  • Autoantigens
  • Receptors, Interleukin-2
  • Transcription Factors