Strong expression of CD134 (OX40), a member of the TNF receptor family, in a T helper 2-type cytokine environment.
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.
Department of Pathology, Academic Medical Center, University of Amsterdam, The Netherlands.
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Roos
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Schilder-Tol
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Weening
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Aten
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology* / Q000502:physiology; D004357:Drug Synergism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007371:Interferon-gamma / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology*; D015759:Ionomycin / Q000494:pharmacology; D008627:Mercuric Chloride / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D051381:Rats; D011914:Rats, Inbred BN; D011971:Receptors, Immunologic / Q000235:genetics; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D019311:Staurosporine / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D047428:Protein Kinase Inhibitors; D011971:Receptors, Immunologic; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; C505718:Tnfrsf4 protein, rat; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D008627:Mercuric Chloride; D015759:Ionomycin; D007371:Interferon-gamma; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate