Abstract
Ags characterizing tumors or chronic viral infection are generally presented to the host immune system before specific immunotherapy is initiated, and consequent generation of regulatory CD4(+) T cells can inhibit induction of desired effector CD8 T cell responses. IL-10 produced in response to ongoing Ag exposure inhibits generation of CD8 T cells in an Ag-experienced host. We now show that this IL-10 is produced by Ag experienced CD4(+) glucocorticoid-induced tumor necrosis factor receptor(+) T cells that also secrete IFN-gamma upon antigenic stimulation, that IL-10 secretion by these cells is enhanced through IFN-gamma signaling, and, unexpectedly, that IFN-gamma signaling is required for inhibition of generation of Ag-specific CD8 T cell responses in an Ag-experienced host. Systemic inhibition of both IL-10 and IFN-gamma at the time of immunization may therefore facilitate induction of effective immunotherapeutic responses against tumor specific and viral Ags.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bovine papillomavirus 1 / immunology
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CD4 Antigens / physiology
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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 / virology
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Capsid Proteins / administration & dosage
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Capsid Proteins / immunology
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Cytotoxicity, Immunologic / immunology*
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Female
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Immunosuppression Therapy
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Interferon-gamma / metabolism
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Interferon-gamma / physiology*
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Interleukin-10 / biosynthesis
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Interleukin-10 / metabolism*
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Interleukin-2 Receptor alpha Subunit / physiology
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Lymph Nodes / immunology
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Lymph Nodes / metabolism
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Lymph Nodes / virology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Tumor Necrosis Factor / biosynthesis
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Signal Transduction / immunology
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism*
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T-Lymphocytes, Regulatory / virology
Substances
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CD4 Antigens
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Capsid Proteins
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Interleukin-2 Receptor alpha Subunit
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Receptors, Tumor Necrosis Factor
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Interleukin-10
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Interferon-gamma