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.