Abstract
It is uncertain whether NK cells modulate T cell memory differentiation. By using a genetic model that allows the selective depletion of NK cells, we show in this study that NK cells shape CD8(+) T cell fate by killing recently activated CD8(+) T cells in an NKG2D- and perforin-dependent manner. In the absence of NK cells, the differentiation of CD8(+) T cells is strongly biased toward a central memory T cell phenotype. Although, on a per-cell basis, memory CD8(+) T cells generated in the presence or the absence of NK cells have similar functional features and recall capabilities, NK cell deletion resulted in a significantly higher number of memory Ag-specific CD8(+) T cells, leading to more effective control of tumors carrying model Ags. The enhanced memory responses induced by the transient deletion of NK cells may provide a rational basis for the design of new vaccination strategies.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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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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Cells, Cultured
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Coculture Techniques
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Female
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Humans
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Immunologic Memory* / genetics
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Killer Cells, Natural / pathology
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Lymphocyte Activation / genetics
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Lymphocyte Activation / immunology*
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Lymphocyte Depletion / methods*
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Melanoma, Experimental / immunology
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Melanoma, Experimental / metabolism
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Melanoma, Experimental / pathology
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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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NK Cell Lectin-Like Receptor Subfamily K / deficiency
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NK Cell Lectin-Like Receptor Subfamily K / metabolism
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NK Cell Lectin-Like Receptor Subfamily K / physiology
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Perforin
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Pore Forming Cytotoxic Proteins / biosynthesis
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Pore Forming Cytotoxic Proteins / genetics
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Pore Forming Cytotoxic Proteins / physiology
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Up-Regulation / genetics
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Up-Regulation / immunology*
Substances
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Klrk1 protein, mouse
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NK Cell Lectin-Like Receptor Subfamily K
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PRF1 protein, human
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Pore Forming Cytotoxic Proteins
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Perforin