Abstract
Interferon (IFN)-gamma is a pleiotropic cytokine with a central role in innate and adaptive immunity. As a potent pro-inflammatory and antitumor cytokine, IFN-gamma is conventionally thought to be responsible for driving cellular immune response. On the other hand, accumulating evidence suggests that IFN-gamma also has immunosuppressive activity. An important role for IFN-gamma in inhibiting graft-versus-host disease (GVHD) has been demonstrated in murine models, despite IFN-gamma being one of the key factors amplifying T cell activation during the process of acute GVHD (aGVHD), the major complication and cause of post-transplant mortality in allogeneic bone marrow transplantation (BMT). At the same time, IFN-gamma facilitates graft-versus-leukemia (GVL) activity. Dissociation of GVL effects from GVHD has been the ultimate goal of allogeneic BMT in the treatment of hematologic malignancies. This paradoxic role of IFN-gamma makes modulating its activity a promising strategy to maximize GVL while minimizing GVHD and improve clinical outcomes in BMT. In this review, the effects of IFN-gamma on GVHD and GVL are discussed with consideration of the mechanism of IFN-gamma action.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Antigen-Presenting Cells / transplantation
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Bone Marrow Transplantation / immunology*
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Drug Administration Schedule
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Enzyme Induction / drug effects
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Graft vs Host Disease / immunology*
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Graft vs Host Disease / prevention & control
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Graft vs Leukemia Effect / immunology*
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Humans
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Immunologic Factors / administration & dosage
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Immunologic Factors / pharmacology
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Immunologic Factors / therapeutic use
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Immunosuppressive Agents / administration & dosage
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Immunosuppressive Agents / pharmacology
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Immunosuppressive Agents / therapeutic use
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Indoleamine-Pyrrole 2,3,-Dioxygenase / biosynthesis
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Indoleamine-Pyrrole 2,3,-Dioxygenase / deficiency
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Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
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Interferon-gamma / administration & dosage
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Interferon-gamma / immunology
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Interferon-gamma / pharmacology
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Interferon-gamma / physiology*
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Interferon-gamma / therapeutic use
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Killer Cells, Natural / metabolism
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Leukemia, Experimental / drug therapy
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Leukemia, Experimental / immunology
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Leukemia, Experimental / surgery
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Mesenchymal Stem Cells / metabolism
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Mice
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Mice, Knockout
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Natural Killer T-Cells / metabolism
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T-Lymphocyte Subsets / metabolism
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Transplantation, Homologous / immunology
Substances
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Immunologic Factors
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Immunosuppressive Agents
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Indoleamine-Pyrrole 2,3,-Dioxygenase
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Interferon-gamma