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 C D134 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 acti vation. CD134 expression could be induced by interleukin-4, but not by interferon-gamma or tumor necrosis factor-alpha. Effects of interleuk in-4 and of phorbol 12-myristate 13-acetate on CD134 expression could be blocked by the protein kinase inhibitor staurosporin. Combination o f these stimuli with ionomycin resulted in a strongly synergistic incr ease of CD134, expression, which was blocked by the calcineurin-inhibi tor cyclosporin A. The results demonstrate the involvement of two syne rgistically acting pathways in induction of CD134 expression. Furtherm ore, they suggest a role for interleukin-4 in induction of CD134 expre ssion in vivo.