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Biol Blood Marrow Transplant. 2017 Nov;23(11):1852-1860. doi: 10.1016/j.bbmt.2017.07.016. Epub 2017 Jul 24.

Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease.

Author information

1
Department of Pathology, University of California San Diego, La Jolla, California.
2
Department of Pediatrics, University of California San Diego, La Jolla, California.
3
Center for Computational Biology and Bioinformatics, University of California San Diego, La Jolla, California.
4
Department of Medicine, University of California San Diego, La Jolla, California.
5
Department of Pathology, University of California San Diego, La Jolla, California. Electronic address: gpmorris@ucsd.edu.

Abstract

Defective post-transplantation thymopoiesis is associated with chronic graft-versus-host disease (GVHD), a multiorgan pathology affecting up to 80% of patients after allogeneic hematopoietic stem cell transplantation (HSCT). Previous work demonstrated that the subset of T cells expressing 2 T cell receptors (TCRs) is predisposed to alloreactivity, driving selective and disproportionate activity in acute GVHD in both mouse models and HSCT patients. Here we investigate a potential role for this pathogenic T cell subset in chronic GVHD (cGVHD). HSCT patients with cGVHD demonstrated increased numbers of dual TCR cells in circulation. These dual receptor cells had an activated phenotype, indicating an active role in cGVHD. Notably, single-cell RNA sequencing identified the increased dual TCR cells in cGVHD as predominantly expressing Tbet, indicative of a proinflammatory phenotype. These results identify dual TCR cells as specific mediators of pathogenic inflammation underlying cGVHD and highlight Tbet-driven T cell function as a potential pathway for potential therapeutic targeting.

KEYWORDS:

Chronic graft-versus-host disease; T cell; T cell receptor; TCR

PMID:
28750779
PMCID:
PMC5682197
DOI:
10.1016/j.bbmt.2017.07.016
[Indexed for MEDLINE]
Free PMC Article

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