Abstract
T helper 1 (TH1) cells mediate cellular immunity, whereas TH2 cells potentiate antiparasite and humoral immunity. We used a complementary DNA subtraction method, representational display analysis, to show that the small guanosine triphosphatase Rac2 is expressed selectively in murine TH1 cells. Rac induces the interferon-gamma (IFN-gamma) promoter through cooperative activation of the nuclear factor kappa B and p38 mitogen-activated protein kinase pathways. Tetracycline-regulated transgenic mice expressing constitutively active Rac2 in T cells exhibited enhanced IFN-gamma production. Dominant-negative Rac inhibited IFN-gamma production in murine T cells. Moreover, T cells from Rac2-/- mice showed decreased IFN-gamma production under TH1 conditions in vitro. Thus, Rac2 activates TH1-specific signaling and IFN-gamma gene expression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cells, Cultured
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Cytokines / biosynthesis
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Cytokines / genetics
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Gene Expression Regulation
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Humans
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Interferon-gamma / biosynthesis
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Interferon-gamma / genetics*
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JNK Mitogen-Activated Protein Kinases
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Jurkat Cells
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Lymphocyte Activation
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Mice
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Mice, Transgenic
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Mitogen-Activated Protein Kinases / metabolism
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NF-kappa B / metabolism
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Promoter Regions, Genetic
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RAC2 GTP-Binding Protein
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Signal Transduction
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Th1 Cells / cytology
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Th1 Cells / immunology*
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Th1 Cells / metabolism*
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Transfection
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p38 Mitogen-Activated Protein Kinases
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism*
Substances
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Cytokines
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NF-kappa B
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Interferon-gamma
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JNK Mitogen-Activated Protein Kinases
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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rac GTP-Binding Proteins