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

J Clin Invest. 2020 Sep 1;130(9):4624-4636. doi: 10.1172/JCI129965.


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.

Keywords: Bone marrow transplantation; Immunology; T cells; Transplantation.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Allografts
  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / pathology
  • Female
  • Graft vs Host Disease / immunology*
  • Graft vs Host Disease / pathology
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Interferon-gamma / immunology
  • Interleukin-17 / immunology
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Prospective Studies
  • Skin / immunology*
  • Skin / pathology
  • Skin Diseases / immunology*
  • Skin Diseases / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology


  • IFNG protein, human
  • Interleukin-17
  • Interferon-gamma