NIH VideoCast - Going rogue: Aire and the enforcement of immune tolerance

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Going rogue: Aire and the enforcement of immune tolerance

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Air date:	Wednesday, October 5, 2016, 4:15:00 PM Time displayed is Eastern Time, Washington DC Local
Views:	Total views: 263 (43 Live, 220 On-demand)
Category:	Immunology
Runtime:	01:08:25
Closed captioning:	Check box to display CC outside of the video Note: You can drag the captioning window around and resize it
Description:	Immunology Interest Group Seminar Series 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 are directed into the Treg cell lineage; dysregulation of this process results in the diversion of Treg cell-biased clonotypes into pathogenic conventional T cells.

NLM Title:	Going rogue : aire and the enforcement of immune tolerance / Dr. Peter Savage.
Author:	Savage, Peter. National Institutes of Health (U.S.). Immunology Interest Group,
Publisher:
Abstract:	(CIT): 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 are directed into the Treg cell lineage; dysregulation of this process results in the diversion of Treg cell-biased clonotypes into pathogenic conventional T cells.
Subjects:	Autoimmunity--genetics Immune Tolerance--immunology Neoplasms--immunology Polyendocrinopathies, Autoimmune--immunology T-Lymphocytes, Regulatory--immunology
Publication Types:	Lecture Webcast

NLM Classification:	WD 305
NLM ID:	101696068
CIT Live ID:	18520
Permanent link:	https://videocast.nih.gov/watch=18520

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