Graft-versus-host disease and the Th1/Th2 paradigm

Graft-versus-host disease (GVHD) is the major complication after allogeneic bone marrow transplantation (BRIT) 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 BRIT, 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 BRIT 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 BRIT and thus avoid the increased risk of relapse of malignancy and impairment of donor cell engraftment.