Abstract
Injection of agonistic anti-CD40 Abs into mice has been shown to amplify weak CD8 T cell responses to poorly immunogenic compounds and to convert T cell tolerance to T cell priming. In this study we demonstrate that anti-CD40 treatment of C57BL/6 mice, without Ag delivery, led to a marked increase in the number of memory phenotype CD4 and CD8 T cells. Adoptive transfer experiments using CD40-deficient hosts further revealed that the proliferative response of memory T cells, induced by systemic CD40 signaling, was dependent on CD40 expression of host APCs. CD40 ligation in vivo induced vigorous cell division of both memory phenotype and bona fide virus-specific memory CD8 T cells in a partially IL-15-dependent manner. However, only memory phenotype, but not Ag-experienced memory CD8 T cells increased in cell number after anti-CD40 treatment in vivo. Taken together our data show that activation of APC via CD40 induces a marked bystander proliferation of memory phenotype T cells. In addition, we demonstrate that bona fide Ag-experienced memory CD8 T cells respond differently to anti-CD40-induced signals than memory phenotype CD8 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, Monoclonal / administration & dosage
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Antibodies, Monoclonal / metabolism
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Bystander Effect / immunology*
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CD40 Antigens / immunology*
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CD40 Antigens / metabolism*
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CD40 Antigens / physiology
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / immunology
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Cell Division / immunology
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CpG Islands / immunology
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Cytokines / physiology
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Female
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Hyaluronan Receptors / biosynthesis
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Immunologic Memory*
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Immunophenotyping*
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Injections, Intraperitoneal
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Interferon-gamma / biosynthesis
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Lectins, C-Type
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Ligands
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Lipopolysaccharides / pharmacology
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Lymphocyte Activation / immunology
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Lymphocyte Count
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Oligodeoxyribonucleotides / pharmacology
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Poly I-C / pharmacology
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Receptors, Immunologic / biosynthesis
Substances
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Antibodies, Monoclonal
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CD40 Antigens
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CPG-oligonucleotide
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Cytokines
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Hyaluronan Receptors
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Klrg1 protein, mouse
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Lectins, C-Type
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Ligands
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Lipopolysaccharides
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Oligodeoxyribonucleotides
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Receptors, Immunologic
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Interferon-gamma
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Poly I-C