Abstract
The role of costimulation has previously been confined to the very early stages of the CD8+ T cell response. In this study, we demonstrate the requirement for CD27 costimulation during the later phase, but not programming of the primary CD8+ T cell response to influenza virus and reveal a novel mechanism of action for CD27 costimulation. CD27 signals, during the later phase of the primary CD8+ T cell response, prevent apoptosis of Ag-specific CD8+ T cells. Blocking CD27L (CD70) on days 6 and 8 after infection reduces the number of NP(366-374)-specific CD8+ T cells, increases their sensitivity to CD95/Fas-mediated apoptosis, and up-regulates FasL on CD4+ T cells. This reduction of NP(366-374)-specific CD8+ T cells requires the presence of CD4+ T cells and Fas signaling. Lack of CD27 signals also decreases the quality of memory CD8+ T cell responses. Memory CD8+ T cells, which express surface CD27 similar to naive cells, however, do not require CD27 costimulation during a secondary response. Thus, CD27 acts indirectly to regulate primary Ag-specific CD8+ T cell responses by preventing apoptosis of CD8+ T cells during the later phase of the primary response and is required for optimal quality of memory cells, but is not required during normally primed secondary CD8+ T cell responses.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Adoptive Transfer
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Animals
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Antibodies, Blocking / metabolism
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Antibodies, Monoclonal / metabolism
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Apoptosis / genetics
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Apoptosis / immunology*
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CD27 Ligand / antagonists & inhibitors
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CD27 Ligand / immunology
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CD27 Ligand / metabolism
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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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CD8-Positive T-Lymphocytes / virology
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Immunization, Secondary
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Immunologic Memory / genetics
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Influenza A virus / immunology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Orthomyxoviridae Infections / immunology
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Orthomyxoviridae Infections / metabolism
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Orthomyxoviridae Infections / virology
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology
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Signal Transduction / genetics
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Signal Transduction / immunology*
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Time Factors
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / deficiency
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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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Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology*
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Viral Core Proteins / administration & dosage
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Viral Core Proteins / immunology
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fas Receptor / biosynthesis
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fas Receptor / deficiency
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fas Receptor / genetics
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fas Receptor / physiology*
Substances
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Antibodies, Blocking
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Antibodies, Monoclonal
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CD27 Ligand
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Cd70 protein, mouse
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Peptide Fragments
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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Viral Core Proteins
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fas Receptor
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nucleoprotein (366-374), influenza virus