Graft-versus-host disease: host and donor views.
Major histocompatibility complex (MHC) antigens, termed HLA in man, provide the major barrier to transplantation. Clinical manifestations of the host-versus-graft reaction are generally referred to as rejection and those of the graft-versus-host (GVH) reaction as graft-versus-host disease (GVHD). GVHD can occur after transplantation of marrow or solid organs or transfusion of blood products. GVHD involves antigen-presenting cells, which are recognized by T lymphocytes via the T-cell receptor. CD4 and CD8 serve as accessory molecules. This interaction results in T-cell activation, expression of interleukin-2 receptors (IL-2R) and the production of IL-2 followed, generally, by clonal proliferation and differentiation associated with lymphokine secretion and dysregulation that may involve interferon-gamma; tumor necrosis factor-alpha; IL-2, -3, -4, -5, -6, and -9; granulocyte macrophage colony-stimulating factor (GM-CSF); and other factors. Effector cells such as cytotoxic T cells, natural killer (NK) cells, and macrophages become activated, mostly by bone marrow-derived lymphohemopoietic cells, and contribute to cell and tissue death. Many of the cytokines also alter vascular endothelium; conceivably these changes also affect homing of cells and allogeneic interactions. Another factor is the administration of in vivo GVHD prophylaxis, which may modify both undesirable (GVHD-inducing) and desirable (tolerance-inducing) mechanisms. Exogenous hematopoietic growth factors and cytokines recently introduced into clinical trials may interfere with endogenous feedback loops in a positive or negative fashion. Adverse reactions have been observed with IL-2 and with interferon. Potentially beneficial effects have been reported with the use of soluble IL-1R or IL-1R-antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Deeg
H J
HJ
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
D006086:Graft vs Host Disease / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D006680:HLA Antigens / Q000097:blood; D006801:Humans; D014019:Tissue Donors
D006680:HLA Antigens