Journal
JOURNAL OF IMMUNOLOGY
Volume 199, Issue 1, Pages 33-38Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1700406
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Funding
- National Institutes of Health [R21 AI101540, R01 AI106791, 5U24-AI118635, P01 AI35296, T32 HL007741, T32 AI007313, T32 GM008244]
- American Association of Immunologists Careers in Immunology Fellowship
- University of Minnesota Office of the Vice President for Research fellowship
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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 TCRa and beta (TCR alpha(+/-) beta(+/-)) loci, rendering them incapable of producing dual TCR T cells. We found that the lack of dual TCR alpha expression skewed the insulin-specific thymocyte population toward greater regulatory T (T-reg) cell commitment, resulting in a more tolerogenic T-reg 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-reg cell lineage.
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