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Annals of Hematology
Published in: Annals of Hematology 9/2004

01-09-2004 | Review Article

Immunopathogenesis of acute graft-versus-host disease: implications for novel preventive and therapeutic strategies

Authors: Robert Zeiser, Reinhard Marks, Hartmut Bertz, Jürgen Finke

Published in: Annals of Hematology | Issue 9/2004

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Abstract

Acute graft-versus-host disease (GVHD) is a primary T-cell-mediated complication of allogeneic hematopoietic stem cell transplantation (HSCT), occurring when donor-derived T cells are stimulated by host antigen-presenting cells (APCs), enhanced by proinflammatory cytokines such as interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha. Recent data indicate that besides differences in major histocompatibility and minor histocompatibility antigens, cytokine gene polymorphisms have a predictive value for the complication of GVHD. Patients with a high anti-inflammatory IL-10 production have been demonstrated to be protected from GVHD while patients with high TNF-alpha serum levels were more at risk for GVHD. Pharmacological immunosuppression for GVHD prophylaxis and therapy, including unspecific approaches with corticosteroids or methotrexate (MTX), as well as more specific therapy with cyclosporin A (CsA), tacrolimus (FK506), sirolimus, mycophenolate mofetil (MMF), antithymocyte globulin (ATG), and monoclonal antibodies (MAbs) directed against CD3, CD25, CD52, cytotoxic T-lymphocyte antigen (CTLA)-4, CD40 ligand, or TNF-alpha, have been proven to be effective. Recent data on novel techniques to selectively deplete alloreactive T cells by removal, destruction, or anergy induction while preserving leukemia-specific T-cell clones suggest a clinical benefit from these approaches. Gene-modified T cells that can selectively be depleted and CD4+CD25+ regulatory T cells are under investigation for their ability to modulate alloreactivity after HSCT. With a better understanding of the immunopathogenesis of acute GVHD and the technical improvement of recently described therapeutic approaches, such as removal of naive T cells, selection of Th2 cells, suicide gene transduced T cells, and adoptive transfer of regulatory T cells, the use of alloreactivity as a treatment modality may be expanded to nonhematological disease entities such as solid tumors or autoimmune disorders.
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Metadata
Title
Immunopathogenesis of acute graft-versus-host disease: implications for novel preventive and therapeutic strategies
Authors
Robert Zeiser
Reinhard Marks
Hartmut Bertz
Jürgen Finke
Publication date
01-09-2004
Publisher
Springer-Verlag
Published in
Annals of Hematology / Issue 9/2004
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-004-0890-7

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