Abstract
Allogeneic hematopoietic cell transplantation represents an important therapy for certain malignant and nonmalignant diseases. However, graft-versus-host disease (GVHD) is a major cause of mortality and morbidity. The search for agents that can efficiently suppress GVHD has been going on for more than half a century. GVHD is particularly strong in xenogeneic donor-recipient combinations, given the unlimited number of potentially immunogenic antigens donor lymphocytes encounter in the host. Using a hu-nonobese diabetic/severe combined immunodeficiency (hu-NOD/SCID) gamma-null model of xenogeneic GVHD, we have demonstrated that treatment with recombinant immunoglobulin-like transcript 3-Fc protein induces the differentiation of CD8(+) T suppressor cells and blocks the cellular and humoral arm of the GVH reaction.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Heterophile / immunology
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Antigens, Heterophile / immunology
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / pathology
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Cell Differentiation / genetics
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Disease Progression
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Female
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Genetic Engineering
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Graft vs Host Disease / immunology*
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Graft vs Host Disease / physiopathology
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Graft vs Host Disease / therapy
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Hematopoietic Stem Cell Transplantation
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Humans
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Immunoglobulin Fc Fragments / genetics
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Immunoglobulin Fc Fragments / immunology
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Immunoglobulin Fc Fragments / metabolism*
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Immunosuppressive Agents / immunology
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Immunosuppressive Agents / metabolism
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Immunotherapy*
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Membrane Glycoproteins
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Mice
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Mice, Inbred NOD
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Mice, SCID
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Radiation Chimera
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / immunology
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Receptors, Cell Surface / metabolism*
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Receptors, Immunologic
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism*
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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T-Lymphocytes, Regulatory / pathology
Substances
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Antibodies, Heterophile
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Antigens, Heterophile
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Immunoglobulin Fc Fragments
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Immunosuppressive Agents
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LILRB4 protein, human
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Membrane Glycoproteins
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Receptors, Cell Surface
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Receptors, Immunologic
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Recombinant Fusion Proteins