Immunologic Research

, Volume 15, Issue 1, pp 50–73 | Cite as

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

  • Werner Krenger
  • James L. M. Ferrara
Original Paper


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-γ) 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-α, 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.

Key Words

Graft-versus-host disease T cell cytokines Bone marrow transplantation Th1/Th2 dichotomy 


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Copyright information

© Humana Press Inc. 1996

Authors and Affiliations

  • Werner Krenger
    • 1
    • 2
  • James L. M. Ferrara
    • 1
    • 2
  1. 1.Division of Pediatric OncologyDana-Farber Cancer Institute and Children's HospitalBoston(USA)
  2. 2.Department of PediatricsHarvard Medical SchoolBostonUSA

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