| First Author | Malchow S | Year | 2016 |
| Journal | Immunity | Volume | 44 |
| Issue | 5 | Pages | 1102-13 |
| PubMed ID | 27130899 | Mgi Jnum | J:254633 |
| Mgi Id | MGI:6112258 | Doi | 10.1016/j.immuni.2016.02.009 |
| Citation | Malchow S, et al. (2016) Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage. Immunity 44(5):1102-13 |
| abstractText | 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. |
