title: Etiology of GVHD: alloreactivity or impaired cellular adaptation?
abstract: 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.
authors.affiliation: Department of Microbiology & Immunology, Virginia Commonwealth University School of Medicine , Massey Cancer Center, Richmond, VA , USA .
authors.forename: Masoud H
authors.initials: MH
authors.lastname: Manjili
authors.forename: Amir A
authors.initials: AA
authors.lastname: Toor
mesh_terms: D000222:Adaptation, Physiological / Q000276:immunology; D000818:Animals; D001324:Autoantigens / Q000276:immunology; D006086:Graft vs Host Disease / Q000276:immunology*; D006706:Homeostasis; D006801:Humans; D007113:Immunity, Innate; D007519:Isoantigens / Q000276:immunology*; D051379:Mice; D009928:Organ Specificity / Q000276:immunology; D033581:Stem Cell Transplantation
chemical_list: D001324:Autoantigens; D007519:Isoantigens
keywords: Alloreactivity; T lymphocytes; graft versus host disease; hematopoietic stem cell transplantation; leukemia