Abstract
Blockade of CD40-CD154 interactions can facilitate long-term allograft acceptance in selected rodent and in primate models, but, due to the ability of CD154-independent CD8(+) T cells to initiate graft rejection, this strategy is not always effective. In this work we demonstrate that blockade of the CD40-CD154 pathway at the time of transplantation enables the generation of donor alloantigen-specific CD4(+)CD25(+) regulatory T cells, and that if the regulatory cells are present in sufficient numbers they can suppress allograft rejection mediated by CD154-independent CD8(+) T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Monoclonal / therapeutic use*
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CD4 Antigens / biosynthesis
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / transplantation
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CD40 Antigens / immunology
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CD40 Ligand / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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Epitopes, T-Lymphocyte / immunology*
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Graft Rejection / immunology
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Graft Rejection / prevention & control*
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Heart Transplantation / immunology
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Injections, Intraperitoneal
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C57BL
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Mice, Inbred CBA
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Mice, Inbred NZB
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Mice, Knockout
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Mice, Transgenic
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Receptors, Interleukin-2 / biosynthesis
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Skin Transplantation / immunology
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T-Lymphocyte Subsets / immunology*
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / transplantation
Substances
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Antibodies, Monoclonal
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CD4 Antigens
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CD40 Antigens
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Epitopes, T-Lymphocyte
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Receptors, Interleukin-2
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CD40 Ligand