Roos A, Claessen N, Schilder-Tol E J, Chand M A, Weening J J, Aten J
Department of Pathology, University of Amsterdam, The Netherlands.
Biochem Biophys Res Commun. 1997 Nov 17;240(2):452-7. doi: 10.1006/bbrc.1997.7679.
CD134 (OX40), a member of the tumour necrosis factor receptor family, is expressed on activated T cells and mediates T and B cell costimulation. Its expression is increased after exposure to the thiol-binding compound HgCl2 in BN rats, but not in Lewis rats, in association with induction of a T cell-dependent systemic autoimmune syndrome only in BN rats. Intracellular thiols are involved in regulation of activation and death in T lymphocytes. Therefore, we examined intracellular thiol levels in CD134-defined T cell subsets from BN and Lewis rats. Levels of total thiols and glutathione (GSH) were significantly higher in CD134+CD4+ cells than in CD134+CD4+ cells in both strains. In Lewis rats, total thiol levels in CD4+CD134+ cells, but not in CD4+CD134+ cells, were higher than in BN rats. In contrast, BN rats showed higher GSH levels in CD4+CD134+ cells, but not in CD4+CD134+ cells. In vitro exposure to HgCl2 decreased intracellular thiol levels, predominantly in CD4+CD134+ cells. Furthermore, HgCl2-induced enrichment of CD134+ viable cells was inversely correlated to HgCl2-induced cell death. Strain-dependent differences in thiol levels in CD134-defined subsets of CD4+ lymphocytes and subset-specific modification of thiol levels may contribute to differential lymphocyte activation by oxidizing chemicals.
CD134（OX40）是肿瘤坏死因子受体家族的成员，在活化的T细胞上表达，并介导T细胞和B细胞的共刺激。在BN大鼠中，暴露于硫醇结合化合物氯化汞后其表达增加，但在Lewis大鼠中则不然，且仅在BN大鼠中会诱导T细胞依赖性全身性自身免疫综合征。细胞内硫醇参与T淋巴细胞活化和死亡的调节。因此，我们检测了BN和Lewis大鼠中由CD134定义的T细胞亚群的细胞内硫醇水平。在两个品系中，CD134 + CD4 +细胞中的总硫醇和谷胱甘肽（GSH）水平均显著高于CD134 - CD4 +细胞。在Lewis大鼠中，CD4 + CD134 +细胞而非CD4 + CD134 -细胞中的总硫醇水平高于BN大鼠。相反，BN大鼠的CD4 + CD134 -细胞而非CD4 + CD134 +细胞中GSH水平更高。体外暴露于氯化汞会降低细胞内硫醇水平，主要是在CD4 + CD134 +细胞中。此外，氯化汞诱导的CD134 +活细胞富集与氯化汞诱导的细胞死亡呈负相关。CD134定义的CD4 +淋巴细胞亚群中硫醇水平的品系依赖性差异以及硫醇水平的亚群特异性改变可能导致氧化化学物质对淋巴细胞活化的差异。
