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The cellular mechanism of Aire control of T cell tolerance

Mark S Anderson1, Emily S Venanzi, Zhibin Chen

  • 1Section on Immunology and Immunogenetics, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215, USA.

Immunity
|August 23, 2005
PubMed

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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