Abstract
Stimulation of CD27, a member of the tumour necrosis factor receptor family, by its ligand CD70 induces expansion of IFNgamma secreting CD4+ and CD8+ T cells in vivo. We here analysed the mechanisms through which CD27 mediates this effect. CD27 co-stimulation induced cell division but did not directly instruct naive CD4+ T cells to differentiate into IFNgamma-producing Th1 cells. Rather, in concert with signals delivered through the TCR-CD3 complex, CD27 co-stimulation enhanced the Th1-specific transcription factor T-bet and caused up-regulation of the IL-12Rbeta2 chain. Consequently, CD27-costimulated T cells yielded vast numbers of IFNgamma-secreting cells in response to IL-12. Additionally, CD27 ligation induced a strong up-regulation of Bcl-xL, but not of related anti-apoptotic molecules. Thus, CD27-CD70 interactions may promote Th1 formation by permitting naive T cells to respond to differentiation signals and by promoting survival of activated effector T cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3T3 Cells
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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Antigens, CD / genetics
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Antigens, CD / metabolism
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CD27 Ligand / genetics
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CD27 Ligand / metabolism*
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CD3 Complex / immunology
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / metabolism
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Cell Differentiation / drug effects
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Cell Differentiation / immunology
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Cell Proliferation / drug effects
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Flow Cytometry
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Gene Expression Profiling
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Humans
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Interferon-gamma / genetics
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Interferon-gamma / metabolism
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Interleukin-12 / pharmacology*
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Interleukin-12 Receptor beta 2 Subunit / genetics
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Interleukin-12 Receptor beta 2 Subunit / metabolism
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Interleukin-4 / metabolism
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Interleukin-4 / pharmacology
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Mice
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Protein Binding
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T-Box Domain Proteins / genetics
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T-Box Domain Proteins / metabolism
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Th1 Cells / cytology
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Th1 Cells / immunology*
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Th1 Cells / metabolism
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Transfection
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism*
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bcl-X Protein / genetics
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bcl-X Protein / metabolism
Substances
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Antibodies, Monoclonal
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Antigens, CD
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BCL2L1 protein, human
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CD27 Ligand
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CD3 Complex
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Interleukin-12 Receptor beta 2 Subunit
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T-Box Domain Proteins
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T-box transcription factor TBX21
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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bcl-X Protein
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Interleukin-12
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Interleukin-4
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Interferon-gamma