Etiology of GVHD: alloreactivity or impaired cellular adaptation?

Immunol Invest. 2014;43(8):851-7. doi: 10.3109/08820139.2014.953636.


According to the self-nonself model of immunity, allogeneic T cells are considered as major cause of graft versus host disease (GVHD) following allogeneic stem cell transplantation (SCT). On the other hand, the danger model of immunity suggests that transplant-associated recipient tissue injury rather than donor-derived alloreactive T cells is the main cause of GVHD. What has been less appreciated are the early, both conditioning-dependent and conditioning-independent, events that impair homeostatic cellular adaptations and host-protective immune responses leading to the development of tissue-specific GVHD. The notion of gut injury precipitating in GVHD has been acknowledged by clinicians, with the shift to reduced intensity-conditioning regimens that prevent acute tissue injury and are less disruptive of tissue adaptation to T cell attack. Also, the role of host-protective immune response against pathogens in preventing GVHD has been shown by the lack of severe GVHD in germ free mice as well as an impaired anti-viral immune response during chronic GVHD. This article provides a brief review of the literature on GVHD and suggests that transplant-induced dysregulation of the protective immune response in the recipient of SCT is more important than allogeneic T cells in causing GVHD.

Keywords: Alloreactivity; T lymphocytes; graft versus host disease; hematopoietic stem cell transplantation; leukemia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptation, Physiological / immunology
  • Animals
  • Autoantigens / immunology
  • Graft vs Host Disease / immunology*
  • Homeostasis
  • Humans
  • Immunity, Innate
  • Isoantigens / immunology*
  • Mice
  • Organ Specificity / immunology
  • Stem Cell Transplantation*


  • Autoantigens
  • Isoantigens