Article ID Journal Published Year Pages File Type
3352879 Immunity 2016 12 Pages PDF
Abstract

•Aire impacts the peripheral repertoire of both Treg cells and Tconv cells•The autoimmune defect in Aire−/− mice maps to the Tconv cell compartment•Treg-biased clones are diverted into the Tconv cell subset in Aire−/− mice•Diverted clones dominate the Tconv cell infiltrate in prostatic lesions

SummaryThe 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 differentiate into the Treg cell lineage; dysregulation of this process results in the diversion of Treg cell-biased clonotypes into pathogenic conventional T cells.

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