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Cutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity.


ABSTRACT: Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinity cells preferentially upregulated the TCR-dependent Treg functional mediators IL-10, TIGIT, GITR, and CTLA4, whereas low-affinity cells displayed increased transcripts for Areg and Ebi3, suggesting distinct functional profiles. The results of this study suggest mechanistically distinct and potentially nonredundant roles for high- and low-affinity Tregs in controlling autoimmunity.

SUBMITTER: Sprouse ML 

PROVIDER: S-EPMC5962277 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Cutting Edge: Low-Affinity TCRs Support Regulatory T Cell Function in Autoimmunity.

Sprouse Maran L ML   Shevchenko Ivan I   Scavuzzo Marissa A MA   Joseph Faith F   Lee Thomas T   Blum Samuel S   Borowiak Malgorzata M   Bettini Matthew L ML   Bettini Maria M  

Journal of immunology (Baltimore, Md. : 1950) 20171227 3


Regulatory T cells (Tregs) use a distinct TCR repertoire and are more self-reactive compared with conventional T cells. However, the extent to which TCR affinity regulates the function of self-reactive Tregs is largely unknown. In this study, we used a two-TCR model to assess the role of TCR affinity in Treg function during autoimmunity. We observed that high- and low-affinity Tregs were recruited to the pancreas and contributed to protection from autoimmune diabetes. Interestingly, high-affinit  ...[more]

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