The cellular mechanism of Aire control of T cell tolerance - PubMed (original) (raw)
The cellular mechanism of Aire control of T cell tolerance
Mark S Anderson et al. Immunity. 2005 Aug.
Free article
Abstract
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.
Comment in
- Central tolerance matters.
Goldrath AW, Hedrick SM. Goldrath AW, et al. Immunity. 2005 Aug;23(2):113-4. doi: 10.1016/j.immuni.2005.08.004. Immunity. 2005. PMID: 16111630 Review.
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