Abstract
CD134 (OX40) is involved in T cell costimulation and T cell-dependent antibody production. We show strongly increased T cell expression of CD134 in a model of T helper 2-mediated systemic autoimmunity, induced by HgCl2. Regulation of CD134 expression on CD4+ T cells was further studied in vitro, identifying CD134 as an early marker of T cell activation. CD134 expression could be induced by interleukin-4, but not by interferon-gamma or tumor necrosis factor-alpha. Effects of interleukin-4 and of phorbol 12-myristate 13-acetate on CD134 expression could be blocked by the protein kinase inhibitor staurosporin. Combination of these stimuli with ionomycin resulted in a strongly synergistic increase of CD134 expression, which was blocked by the calcineurin-inhibitor cyclosporin A. The results demonstrate the involvement of two synergistically acting pathways in induction of CD134 expression. Furthermore, they suggest a role for interleukin-4 in induction of CD134 expression in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Autoimmunity* / drug effects
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology*
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Cells, Cultured
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Cytokines / pharmacology*
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Cytokines / physiology
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Drug Synergism
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Female
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / immunology
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Interferon-gamma / pharmacology
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Interleukin-4 / pharmacology*
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Ionomycin / pharmacology
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Mercuric Chloride / pharmacology*
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Protein Kinase Inhibitors
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Rats
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Rats, Inbred BN
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Receptors, Immunologic / genetics
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Receptors, OX40
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Receptors, Tumor Necrosis Factor / genetics
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Recombinant Proteins / pharmacology
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Staurosporine / pharmacology
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Tetradecanoylphorbol Acetate / pharmacology
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Th2 Cells / immunology*
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis
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Tumor Necrosis Factor Receptor Superfamily, Member 7 / genetics*
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Cytokines
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Protein Kinase Inhibitors
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Receptors, Immunologic
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Receptors, OX40
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins
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Tnfrsf4 protein, rat
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Tumor Necrosis Factor Receptor Superfamily, Member 7
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Tumor Necrosis Factor-alpha
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Interleukin-4
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Mercuric Chloride
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Ionomycin
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Interferon-gamma
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Staurosporine
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Tetradecanoylphorbol Acetate