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

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16 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

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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