The immunopathophysiology of acute graft-versus-host-disease

James L.M. Ferrara, Kenneth R. Cooke, Luying Pan, Werner Krenger

Research output: Contribution to journalReview article

Abstract

The major complication after allogeneic bone marrow transplantation (BMT) is the development of graft-versus-host-disease (GVHD). This disease is initiated during the conditioning of the recipient, when host tissues are damaged. During the afferent phase of the disease, alloreactive donor T cells recognize foreign major and minor histocompatibility antigens of host tissues. The efferent phase includes activation of inflammatory effector cells as well as the secretion of cytopathic molecules which induce pathology in skin, gastrointestinal tract, liver, lung, and the immune system. Substantial experimental and clinical evidence now indicates a central role of cytokines in the immunopathophysiology of acute GVHD, which forms the basis of this review. The balance between cytokines released by T helper 1 (Th1) cells (Interleukin 2, interferon-γ) or by T helper 2 (Th2) cells (interleukin 4, interleukin 10) after allogeneic BMT is hypothesized to govern the extent of the systemic inflammatory response. Because Th2 cytokines can inhibit the production of proinflammatory cytokines such as interleukin 1 and tumor necrosis factor-α, a Th1→Th2 shift in the initial response of donor T cells may interrupt the cytokine cascade and thus offer a new approach to the prevention and treatment of acute GVHD. Successful interventions to modify the response of donor T cells may obviate the need for T cell depletion and thereby avoid the increased risk of relapse of malignancy and impairment of donor cell engraftment.

Original languageEnglish (US)
Pages (from-to)473-489
Number of pages17
JournalStem Cells
Volume14
Issue number5
DOIs
StatePublished - Sep 1996
Externally publishedYes

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Keywords

  • Bone marrow transplantation
  • Cytokines
  • Graft-versus-host-disease
  • Review
  • Th1/Th2 cells

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

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