Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease.

The Journal of Clinical Investigation
Sherrie J DivitoThomas S Kupper

Abstract

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT). Donor T cells are key mediators in pathogenesis, but a contribution from host T cells has not been explored, as conditioning regimens are believed to deplete host T cells. To evaluate a potential role for host T cells in GVHD, the origin of skin and blood T cells was assessed prospectively in patients after HSCT in the absence of GVHD. While blood contained primarily donor-derived T cells, most T cells in the skin were host derived. We next examined patient skin, colon, and blood during acute GVHD. Host T cells were present in all skin and colon acute GVHD specimens studied, yet were largely absent in blood. We observed acute skin GVHD in the presence of 100% host T cells. Analysis demonstrated that a subset of host T cells in peripheral tissues were proliferating (Ki67+) and producing the proinflammatory cytokines IFN-γ and IL-17 in situ. Comparatively, the majority of antigen-presenting cells (APCs) in tissue in acute GVHD were donor derived, and donor-derived APCs were observed directly adjacent to host T cells. A humanized mouse model demonstrated that host skin-resident T cells could be activated ...Continue Reading

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Citations

May 27, 2020·The Journal of Clinical Investigation·Laura JardineMatthew Collin
Jun 9, 2021·The Journal of Clinical Investigation·Gérard SociéBruce R Blazar
Aug 15, 2021·Military Medical Research·Ying WangKonrad Fischer
Sep 21, 2021·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Ryotaro YoshidaTakahiro Kubota
Oct 14, 2021·The Journal of Experimental Medicine·Johanna StroblGeorg Stary

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Datasets Mentioned

BETA
AF647

Methods Mentioned

BETA
biopsies
laser-capture microscopy
flow cytometry
biopsy
PCR
confocal microscopy
leukapheresis

Software Mentioned

Photoshop
ImageJ
InFORM

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