Aire Enforces Immune Tolerance by Directing Autoreactive T Cells into the Regulatory T Cell Lineage.
Immunity
; 44(5): 1102-13, 2016 05 17.
Article
em En
| MEDLINE
| ID: mdl-27130899
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Próstata
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Timo
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Fatores de Transcrição
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Autoimunidade
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Subpopulações de Linfócitos T
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Linfócitos T Reguladores
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Tolerância Imunológica
Limite:
Animals
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article