Abstract
In experimental transplantation, blockade of CD40-CD40 ligand (CD40L) interactions has proved effective at permitting long-term graft survival and has recently been approved for clinical evaluation. We show that CD4+ T cell-mediated rejection is prevented by anti-CD40L mAb therapy but that CD8+ T cells remain fully functional. Furthermore, blocking CD40L interactions has no effect on CD8+ T cell activation, proliferation, differentiation, homing to the target allograft, or cytokine production. We conclude that CD40L is not an important costimulatory molecule for CD8+ T cell activation and that following transplantation donor APC can activate recipient CD8+ T cells directly without first being primed by CD4+ T cells.
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, Blocking / administration & dosage
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Antibodies, Monoclonal / administration & dosage
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CD4-Positive T-Lymphocytes / immunology
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CD40 Antigens / metabolism
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CD40 Antigens / physiology*
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CD40 Ligand
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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 / transplantation
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Cell Division / immunology
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Cell Movement / 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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Heart Transplantation / pathology
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Immune Tolerance / immunology
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Injections, Intraperitoneal
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Isoantigens / immunology
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Ligands
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Lymphocyte Activation / immunology*
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / physiology*
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Mice
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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, Transgenic
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Species Specificity
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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CD40 Antigens
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Isoantigens
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Ligands
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Membrane Glycoproteins
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CD40 Ligand