Graft-versus-host disease and the Th1/Th2 paradigm.
Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation (BMT) and is initiated by alloreactive donor T cells recognizing foreign histocompatibility antigens of the host. There is now substantial experimental and clinical evidence to implicate a dysregulation of cytokine networks as a primary cause for the induction and maintenance of GVHD. In this article, current knowledge of the involvement of cytokines in GVHD is reviewed. The balance between type 1 cytokines (interleukin-2, interferon-gamma) and type 2 cytokines (interleukin-4, interleukin-10) is hypothesized to govern the extent to which a cell-mediated immune response and a systemic inflammatory response develop after allogeneic BMT. Because type 2 cytokines can inhibit the production of the proinflammatory cytokines interleukin-1 and tumor necrosis factor-alpha, a type 1 to type 2 shift in the initial response of donor T cells to host alloantigens may interrupt the cytokine cascade after allogeneic BMT and may offer a new approach to the prevention and treatment of acute GVHD. Interventions to specifically eliminate or modify the response of donor T cells to alloantigens in order to reduce GVHD may obviate the need for T cell depletion in clinical BMT and thus avoid the increased risk of relapse of malignancy and impairment of donor cell engraftment.
Krenger
W
W
Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Mass 02115, USA.
Ferrara
J L
JL
D000208:Acute Disease; D000818:Animals; D016026:Bone Marrow Transplantation / Q000009:adverse effects; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology* / Q000628:therapy; D006801:Humans; D008213:Lymphocyte Activation; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014184:Transplantation, Homologous
D016207:Cytokines; D009569:Nitric Oxide