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Peripheral host T cells survive hematopoietic stem cell transplantation and promote graft-versus-host disease
- Source :
- Journal of clinical investigation, 130(9), 4624-4636. The American Society for Clinical Investigation, J Clin Invest
- Publication Year :
- 2020
-
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 :
- 0301 basic medicine
medicine.medical_treatment
Antigen-Presenting Cells
Graft vs Host Disease
Hematopoietic stem cell transplantation
Disease
Proinflammatory cytokine
Pathogenesis
03 medical and health sciences
0302 clinical medicine
immune system diseases
medicine
Humans
Transplantation, Homologous
Host (biology)
business.industry
Macrophages
Hematopoietic Stem Cell Transplantation
General Medicine
medicine.disease
Transplantation
030104 developmental biology
Graft-versus-host disease
surgical procedures, operative
030220 oncology & carcinogenesis
Humanized mouse
Immunology
business
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 00219738
- Database :
- OpenAIRE
- Journal :
- Journal of clinical investigation, 130(9), 4624-4636. The American Society for Clinical Investigation, J Clin Invest
- Accession number :
- edsair.doi.dedup.....654f356f6f62262129341a193eda4753