Abstract
CD8(+) T cell responses have been shown to be regulated by dendritic cells (DCs) and CD4(+) T cells, leading to the tenet that CD8(+) T cells play a passive role in their own differentiation. In contrast, by using a DNA vaccination model, to separate the events of vaccination from those of CD8(+) T cell priming, we demonstrate that CD8(+) T cells, themselves, actively limit their own memory potential through CD8(+) T cell-derived IFN-γ-dependent modification of the IL-12/IL-15Rα axis on DCs. Such CD8(+) T cell-driven cytokine alterations result in increased T-bet and decreased Bcl-2 expression, and thus decreased memory progenitor formation. These results identify an unrecognized role for CD8(+) T cells in the regulation of their own effector differentiation fate and a previously uncharacterized relationship between the balance of inflammation and memory formation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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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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Dendritic Cells / immunology*
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Dendritic Cells / metabolism
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Gene Expression Regulation / immunology
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Humans
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Immunologic Memory*
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Interferon-gamma
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Interleukin-12 / genetics
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Interleukin-12 / immunology
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Interleukin-15 / genetics
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Interleukin-15 / immunology
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Lymphocyte Activation
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Melanoma, Experimental / immunology
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Melanoma, Experimental / prevention & control
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Interleukin-12 / genetics
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Receptors, Interleukin-12 / immunology*
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Receptors, Interleukin-15 / genetics
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Receptors, Interleukin-15 / immunology*
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Signal Transduction / immunology
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Vaccination
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Vaccines, DNA / immunology
Substances
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Interleukin-15
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Receptors, Interleukin-12
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Receptors, Interleukin-15
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Vaccines, DNA
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Interleukin-12
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Interferon-gamma