Immunity
Volume 23, Issue 2, August 2005, Pages 227-239
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Article
The Cellular Mechanism of Aire Control of T Cell Tolerance

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Summary

Aire promotes the tolerization of thymocytes by inducing the expression of a battery of peripheral-tissue antigens in thymic medullary epithelial cells. We demonstrate that the cellular mechanism by which Aire exerts its tolerance-promoting function is not primarily positive selection of regulatory T cells, but rather negative selection of T effector cells. Surprisingly, supplementing its influence on the transcription of genes encoding peripheral-tissue antigens, Aire somehow enhances the antigen-presentation capability of medullary epithelial cells. Thus, this transcriptional control element promotes central tolerance both by furnishing a specific thymic stromal cell type with a repertoire of self antigens and by better arming such cells to present these antigens to differentiating thymocytes. In Aire’s absence, autoimmunity and ultimately overt autoimmune disease develops.

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2

Present address: University of California, San Francisco, Diabetes Center, 513 Parnassus Avenue, Box 0540, San Francisco, California 94143.

3

Present address: Department of Microbiology and Immunology, University of Melbourne, Victoria, 3010, Australia.