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Article
Nature Immunology  4, 350 - 354 (2003)
Published online: 3 March 2003; | doi:10.1038/ni906

Aire regulates negative selection of organ-specific T cells

Adrian Liston1, Sylvie Lesage1, Judith Wilson1, Leena Peltonen2 & Christopher C. Goodnow1

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

2  Department of Medical Genetics and Molecular Medicine, University of Helsinki and National Public Health Institute, Finland.

Correspondence should be addressed to Christopher C. Goodnow chris.goodnow@anu.edu.au
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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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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