Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage
| Autor: | Peter A. Savage, Nicholas D. Socci, Saki Nishi, Daniel S. Leventhal, Victoria Lee, Sven Malchow |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lineage (genetic) Regulatory T cell Immunology FOXP3 chemical and pharmacologic phenomena Biology Autoimmune regulator medicine.disease_cause Article Clonal deletion Autoimmunity Immune tolerance 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Infectious Diseases medicine.anatomical_structure Antigen medicine Immunology and Allergy 030215 immunology |
| Zdroj: | Immunity. 44:1102-1113 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2016.02.009 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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