Cutting edge: Dual TCRa expression poses an autoimmune hazard by limiting regulatory T cell generation

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10 Scopus citations

Abstract

Despite accounting for 10-30% of the T cell population in mice and humans, the role of dual TCR-expressing T cells in immunity remains poorly understood. It has been hypothesized that dual TCR T cells pose an autoimmune hazard by allowing self-reactive TCRs to escape thymic selection. We revisited this hypothesis using the NOD murine model of type 1 diabetes. We bred NOD mice hemizygous at both TCRα and β (TCRα+/- β+/-) loci, rendering them incapable of producing dual TCR T cells.We found that the lack of dual TCRa expression skewed the insulin-specific thymocyte population toward greater regulatory T (Treg) cell commitment, resulting in a more tolerogenic Treg to conventional T cell ratio and protection from diabetes. These data support a novel hypothesis by which dual TCR expression can promote autoimmunity by limiting agonist selection of self-reactive thymocytes into the Treg cell lineage.

Original languageEnglish (US)
Pages (from-to)33-38
Number of pages6
JournalJournal of Immunology
Volume199
Issue number1
DOIs
StatePublished - Jul 1 2017

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health (Grants R21 AI101540 [to B.A.B.], R01 AI106791 [to B.T.F.], 5U24-AI118635 [to B.T.F.], P01 AI35296 [to B.T.F.]), an American Association of Immunologists Careers in Immunology Fellowship (to B.A.B.), and a University of Minnesota Office of the Vice President for Research fellowship (to B.A.B.). N.J.S. acknowledges additional support from National Institutes of Health Grant T32 HL007741. E.R.B. acknowledges support from National Institutes of Health Grants T32 AI007313 and T32 GM008244.

Publisher Copyright:
Copyright © 2017 by The American Association of Immunologists, Inc. All rights reserved.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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