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- Title
Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease.
- Authors
Divito, Sherrie J.; Aasebø, Anders T.; Matos, Tiago R.; Pei-Chen Hsieh; Collin, Matthew; Elco, Christopher P.; O’Malley, John T.; Bækkevold, Espen S.; Reims, Henrik; Gedde-Dahl, Tobias; Hagerstrom, Michael; Hilaire, Jude; Lian, John W.; Milford, Edgar L.; Pinkus, Geraldine S.; Ho, Vincent T.; Soiffer, Robert J.; Kim, Haesook T.; Mihm, Martin C.; Ritz, Jerome
- 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 by donor monocytes to generate a GVHD-like dermatitis. Thus, host tissue-resident T cells may play a previously unappreciated pathogenic role in acute GVHD.
- Subjects
HEMATOPOIETIC stem cell transplantation; T cells; HEMATOPOIETIC stem cells; GRAFT versus host disease; BLOOD cells
- Publication
Journal of Clinical Investigation, 2020, Vol 130, Issue 9, p4624
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI129965