Abstract
IL-18 has been shown to be a strong cofactor for Th1 T cell development. However, we previously demonstrated that when IL-18 was combined with IL-2, there was a synergistic induction of a Th2 cytokine, IL-13, in both T and NK cells. More recently, we and other groups have reported that IL-18 can potentially induce IgE, IgG1, and Th2 cytokine production in murine experimental models. Here, we report on the generation of IL-18-transgenic (Tg) mice in which mature mouse IL-18 cDNA was expressed. CD8+CD44high T cells and macrophages were increased, but B cells were decreased in these mice while serum IgE, IgG1, IL-4, and IFN-gamma levels were significantly increased. Splenic T cells in IL-18 Tg mice produced higher levels of IFN-gamma, IL-4, IL-5, and IL-13 than control wild-type mice. Thus, aberrant expression of IL-18 in vivo results in the increased production of both Th1 and Th2 cytokines.
MeSH terms
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Adjuvants, Immunologic / biosynthesis
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Adjuvants, Immunologic / genetics*
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Adjuvants, Immunologic / physiology*
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Animals
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B-Lymphocytes / cytology
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CD4-CD8 Ratio
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology
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Cell Count
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cells, Cultured
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Gene Expression Regulation / immunology
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Growth Inhibitors / genetics
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Growth Inhibitors / physiology
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Humans
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Immunoglobulin E / blood
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Immunoglobulin G / blood
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Immunophenotyping
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Interferon-gamma / biosynthesis
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Interferon-gamma / blood
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Interleukin-13 / biosynthesis
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Interleukin-18 / biosynthesis
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Interleukin-18 / genetics*
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Interleukin-18 / physiology*
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Interleukin-4 / biosynthesis
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Interleukin-4 / blood
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Interleukin-5 / biosynthesis
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Intracellular Fluid / immunology
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Intracellular Fluid / metabolism
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Macrophages / cytology
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic / immunology*
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Spleen / cytology
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Transgenes / immunology*
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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Adjuvants, Immunologic
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Growth Inhibitors
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Immunoglobulin G
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Interleukin-13
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Interleukin-18
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Interleukin-5
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Interleukin-4
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Immunoglobulin E
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Interferon-gamma