Graft-versus-host disease: how to translate new insights into new therapeutic strategies.
Graft-versus-host disease occurs when transplanted donor-derived T lymphocytes recognize major or minor histocompatibility complex proteins and their associated peptides expressed by recipient antigen-presenting cells. A widely accepted paradigm for the pathophysiology of acute GVHD is based on the existence of 3 sequential steps: (1) injury to the host environment (as would occur during conditioning regimens); (2) donor T-cell activation, proliferation, and differentiation; and (3) damage to the target tissue caused by either cytotoxicity or indirectly by inflammatory cytokines. In order to reduce the incidence of GVHD, recent studies have focused on methods of prophylaxis as well as novel treatments for established GVHD. We review each phase in the development of acute GVHD and discuss recently developed interventions aimed to prevent or treat GVHD by interfering with these pathways.
Devetten
Marcel P
MP
University of Nebraska, 987680 Nebraska Medical Center, Omaha, NE 68198-7680, USA.
Vose
Julie M
JM
D016026:Bone Marrow Transplantation / Q000009:adverse effects; D006086:Graft vs Host Disease / Q000503:physiopathology / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007249:Inflammation; D008213:Lymphocyte Activation; D017710:Lymphocyte Transfusion; D008285:Major Histocompatibility Complex; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation
D007166:Immunosuppressive Agents