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 language | English (US) |
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Pages (from-to) | 33-38 |
Number of pages | 6 |
Journal | Journal of Immunology |
Volume | 199 |
Issue number | 1 |
DOIs | |
State | Published - 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