Abstract
The liver contains abundant cytotoxic cells, including NK-T cells, NK cells, and CTLs. However, the regulation of this cytotoxicity is not fully understood. In this study, we investigated the effect of a recently described cytokine, IL-18, which is present in large quantities in the liver, on the cytotoxicity of intrahepatic lymphocyte subpopulations. This effect of IL-18 was assessed by assaying the in vitro cytotoxicity of purified NK-T, NK, and T cells against a CD95- and perforin-sensitive T cell line, Jurkat. The results show that IL-18 enhances the killing activity of liver NK-T cells by a CD95-independent, perforin-dependent pathway. IL-18 also augments liver NK cell activity, but the exact mechanisms of this killing remain to be elucidated. Finally, the augmentation of the killing activities of liver NK-T and NK cells by IL-18 is not due to soluble TNF-alpha, because none of these cell populations had detectable TNF-alpha production.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adjuvants, Immunologic / physiology*
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Animals
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Cytokines / physiology*
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Cytotoxicity, Immunologic* / genetics
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Humans
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Interferon Inducers / pharmacology
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Interferon-gamma / biosynthesis
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Interleukin-18
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Jurkat Cells
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism
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Liver / cytology
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Liver / immunology*
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Liver / metabolism
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Lymphoproliferative Disorders / genetics
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Lymphoproliferative Disorders / immunology
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Inbred Strains
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Mice, Knockout
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Perforin
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Pore Forming Cytotoxic Proteins
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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Tumor Necrosis Factor-alpha / biosynthesis
Substances
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Adjuvants, Immunologic
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Cytokines
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Interferon Inducers
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Interleukin-18
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Membrane Glycoproteins
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Pore Forming Cytotoxic Proteins
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Tumor Necrosis Factor-alpha
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Perforin
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Interferon-gamma