Going rogue: Aire and the enforcement of immune tolerance

Immunology Interest Group Seminar Series The promiscuous expression of tissue-restricted antigens in the thymus, driven in part by Autoimmune Regulator (Aire), is critical for the protection of peripheral tissues from autoimmune attack. Aire-dependent processes are thought to promote both clonal deletion and the development of Foxp3+ regulatory T (Treg) cells, suggesting that autoimmunity associated with Aire deficiency results from two failed tolerance mechanisms. Here, examination of autoimmune lesions in Aire-/- mice revealed an unexpected third possibility. We found that the predominant conventional T cell clonotypes infiltrating target lesions express antigen receptors that were preferentially expressed by Foxp3+ Treg cells in Aire+/+ mice. Thus, Aire enforces immune tolerance by ensuring that distinct autoreactive T cell specificities are directed into the Treg cell lineage; dysregulation of this process results in the diversion of Treg cell-biased clonotypes into pathogenic conventional T cells.Air date: 10/5/2016 4:15:00 PM
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