Cutting Edge: Dual TCRα Expression Poses an Autoimmune Hazard by Limiting Regulatory T Cell Generation.

Citation data:

Journal of immunology (Baltimore, Md. : 1950), ISSN: 1550-6606, Vol: 199, Issue: 1, Page: 33-38

Publication Year:
2017
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PMID:
28539428
DOI:
10.4049/jimmunol.1700406; 10.3410/f.727650337.793536656; 10.3410/f.727650337.793537228
Author(s):
Schuldt, Nathaniel J; Auger, Jennifer L; Spanier, Justin A; Martinov, Tijana; Breed, Elise R; Fife, Brian T; Hogquist, Kristin A; Binstadt, Bryce A
Publisher(s):
Faculty of 1000, Ltd.; The American Association of Immunologists
Tags:
Immunology and Microbiology
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article description
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 TCRα expression skewed the insulin-specific thymocyte population toward greater regulatory T (T) cell commitment, resulting in a more tolerogenic T 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 T cell lineage.