Abstract
In humans, all alpha beta CD8+ T cells express NKG2D, but in mouse, it is only expressed by activated and memory CD8+ T cells. We purified human naive CD8+ T cells to show that NKG2D serves as a costimulatory receptor for TCR induced Ca2+ mobilization and proliferation. The resulting effector cells are skewed toward a type 1 phenotype and produce high levels of IFN-gamma and TNF-alpha. NKG2D ligands, MHC class I chain-related (MIC)A, MICB, and UL16-binding proteins are expressed on the proliferating cells and NKG2D is down-regulated. The addition of the homeostatic cytokines IL-7 and IL-15 to the culture medium not only enhances proliferation but also counteracts the down-regulation of NKG2D, more so than the addition of IL-2. These results indicate that NKG2D can regulate the priming of human naive CD8+ T cells, which may provide an alternative mechanism for potentiating and channeling the immune response.
MeSH terms
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Animals
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Base Sequence
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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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Calcium Signaling
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Carrier Proteins / genetics
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Carrier Proteins / metabolism
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Cell Proliferation
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DNA, Complementary / genetics
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GPI-Linked Proteins
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Histocompatibility Antigens Class I / genetics
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Histocompatibility Antigens Class I / metabolism
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Humans
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In Vitro Techniques
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Intercellular Signaling Peptides and Proteins
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Interferon-gamma / biosynthesis
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Intracellular Signaling Peptides and Proteins
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Killer Cells, Natural / immunology
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Ligands
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Lymphocyte Activation
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Membrane Proteins
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Mice
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NK Cell Lectin-Like Receptor Subfamily K
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Receptors, Antigen, T-Cell, alpha-beta / metabolism
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Receptors, Immunologic / immunology*
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Receptors, Natural Killer Cell
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Carrier Proteins
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DNA, Complementary
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GPI-Linked Proteins
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Histocompatibility Antigens Class I
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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KLRK1 protein, human
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Klrk1 protein, mouse
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Ligands
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MHC class I-related chain A
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MICB antigen
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Membrane Proteins
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NK Cell Lectin-Like Receptor Subfamily K
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Immunologic
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Receptors, Natural Killer Cell
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Tumor Necrosis Factor-alpha
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ULBP1 protein, human
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ULBP2 protein, human
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ULBP3 protein, human
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Interferon-gamma