Unknown

Dataset Information

0

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


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-? 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.

PROVIDER: S-EPMC7456221 | BioStudies |

REPOSITORIES: biostudies

Similar Datasets

| S-EPMC5000685 | BioStudies
| S-EPMC3335388 | BioStudies
| S-EPMC6423891 | BioStudies
| S-EPMC3139384 | BioStudies
| S-EPMC3265143 | BioStudies
| S-EPMC3031488 | BioStudies
| S-EPMC5617147 | BioStudies
| S-EPMC3731935 | BioStudies
| S-EPMC4311226 | BioStudies
| S-EPMC3780546 | BioStudies