Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage

作者：Malchow Sven; Leventhal Daniel S; Lee Victoria; Nishi Saki; Socci Nicholas D; Savage Peter A

来源：Immunity, 2016, 44(5): 1102-1113.

DOI：10.1016/j.immuni.2016.02.009

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

• 出版日期2016-5-17