Josien R, Wong B R, Li H L, Steinman R M, Choi Y
Laboratory of Cellular Physiology and Immunology, Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10021, USA.
J Immunol. 1999 Mar 1;162(5):2562-8.
TNF-related activation-induced cytokine (TRANCE) is a member of the TNF family recently identified in activated T cells. We report here that TRANCE mRNA is constitutively expressed in memory, but not naive, T cells and in single-positive thymocytes. Upon TCR/CD3 stimulation, TRANCE mRNA and surface protein expression are rapidly up-regulated in CD4+ and CD8+ T cells, which can be further enhanced on CD4+ T cells by CD28-mediated costimulation. However, TRANCE induction is significantly suppressed when cells are stimulated in the presence of IL-4, but is not modified in the presence of IFN-alpha, IFN-gamma, TGF-beta, TNF-alpha, or IL-2. High levels of TRANCE receptor expression are found on mature dendritic cells (DCs). In this study we show that activated T and B cells also express TRANCE receptor, but only at low levels. TRANCE, however, does not exert any significant effect on the proliferation, activation, or survival of those cells. In DCs, TRANCE induces the expression of proinflammatory cytokines (IL-6, IL-1) and T cell growth and differentiation factors (IL-12, IL-15) in addition to enhancing DC survival. Moreover, TRANCE cooperates with CD40 ligand or TNF-alpha to further increase the viability of DCs, suggesting that several TNF-related molecules on activated T cells may cooperatively regulate the function and survival of DCs to enhance T cell-mediated immune responses.
肿瘤坏死因子相关的激活诱导细胞因子(TRANCE)是最近在活化T细胞中发现的肿瘤坏死因子家族成员。我们在此报告,TRANCE mRNA在记忆性T细胞而非初始T细胞以及单阳性胸腺细胞中组成性表达。经TCR/CD3刺激后,TRANCE mRNA和表面蛋白表达在CD4⁺和CD8⁺T细胞中迅速上调,在CD4⁺T细胞上,CD28介导的共刺激可进一步增强这种上调。然而,当细胞在IL-4存在下受到刺激时,TRANCE的诱导被显著抑制,但在IFN-α、IFN-γ、TGF-β、TNF-α或IL-2存在下则无变化。在成熟树突状细胞(DC)上发现高水平的TRANCE受体表达。在本研究中我们表明,活化的T细胞和B细胞也表达TRANCE受体,但仅为低水平。然而,TRANCE对这些细胞的增殖、活化或存活没有任何显著影响。在DC中,TRANCE除了增强DC存活外,还诱导促炎细胞因子(IL-6、IL-1)以及T细胞生长和分化因子(IL-12、IL-15)的表达。此外,TRANCE与CD40配体或TNF-α协同作用,进一步提高DC的活力,这表明活化T细胞上的几种肿瘤坏死因子相关分子可能协同调节DC的功能和存活,以增强T细胞介导的免疫反应。