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

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Abstract

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.

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Authors and Affiliations

  1. Division of Pediatric Oncology, Dana-Farber Cancer Institute and Children's Hospital, 44 Binnev Street, D1638, 02115, Boston, MA, (USA)

    Werner Krenger & James L. M. Ferrara

  2. Department of Pediatrics, Harvard Medical School, Boston, Mass., USA

    Werner Krenger & James L. M. Ferrara

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  1. Werner Krenger
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  2. James L. M. Ferrara
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This work was supported by NIH grants AI 30018 and CA 39542. W.K. is a David Abraham Fellow in Pediatric Oncology. J.L. M.F. is a scholar of the Leukemia Society of America.

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Krenger, W., Ferrara, J.L.M. Graft-versus-host disease and the Th1/Th2 paradigm. Immunol Res 15, 50–73 (1996). https://doi.org/10.1007/BF02918284

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