Abstract
The mechanism(s) by which DNA vaccines trigger the activation of Ag-specific T cells is incompletely understood. A series of in vivo and in vitro experiments indicates plasmid transfection stimulates muscle cells to up-regulate expression of MHC class I and costimulatory molecules and to produce multiple cytokines and chemokines. Transfected muscle cells gain the ability to directly present Ag to CD8 T cells through an IFN-regulatory factor 3-dependent process. These findings suggest that transfected muscle cells at the site of DNA vaccination may contribute to the magnitude and/or duration of the immune response initiated by professional APCs.
MeSH terms
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Animals
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Antigen Presentation / genetics
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Antigen Presentation / immunology
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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 Line
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Cell Line, Tumor
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Cell Movement / genetics
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Cell Movement / immunology
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Epitopes, T-Lymphocyte / immunology
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Histocompatibility Antigens Class I / biosynthesis
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Histocompatibility Antigens Class I / genetics
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Humans
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Interferon Regulatory Factor-3 / physiology
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology
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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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Plasmids
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Quadriceps Muscle / cytology*
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Quadriceps Muscle / immunology*
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Quadriceps Muscle / metabolism
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Transfection* / methods
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Vaccines, DNA / administration & dosage*
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Vaccines, DNA / genetics
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Vaccines, DNA / immunology*
Substances
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Epitopes, T-Lymphocyte
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Histocompatibility Antigens Class I
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IRF3 protein, human
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Interferon Regulatory Factor-3
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Irf3 protein, mouse
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Vaccines, DNA