Format

Send to

Choose Destination
J Immunol. 2017 Jul 1;199(1):33-38. doi: 10.4049/jimmunol.1700406. Epub 2017 May 24.

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

Author information

1
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455.
2
Center for Immunology, University of Minnesota, Minneapolis, MN 55455.
3
Department of Medicine, University of Minnesota, Minneapolis, MN 55455; and.
4
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455.
5
Department of Pediatrics, University of Minnesota, Minneapolis, MN 55455; binstadt@umn.edu.

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 TCRα 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.

PMID:
28539428
PMCID:
PMC5501482
DOI:
10.4049/jimmunol.1700406
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center