Gupta S, Vayuvegula B
Department of Medicine, University of California, Irvine 92717.
J Clin Immunol. 1987 Nov;7(6):486-9. doi: 10.1007/BF00915060.
It is well established that the activation of T lymphocytes by mitogen/antigen is accompanied by a rise in intracellular free calcium ([Ca2+]i), changes in membrane potential, metabolism of inositol phospholipid, and activation of protein kinase C. These early events of signal transduction culminate in late events of lymphocyte activation, namely, DNA synthesis, lymphokine production, and cellular proliferation. In this study we examined the effect of human immunodeficiency virus (HIV) on changes in membrane potential and [Ca2+]i levels. The membrane potentials were markedly decreased (depolarized) in T cell lines infected with HIV (H9/HTLV IIIb) and did not respond normally to phytohemagglutinin (PHA) or anti-T3 (anti-CD3) monoclonal antibody compared to uninfected H9 cell line. The basal [Ca2+]i levels in H9/HTLV IIIb cells were increased in comparison to those in H9 cells; however, there was very little further increase in [Ca2+]i in H9/HTLV IIIb cells following activation with PHA or anti-T3 monoclonal antibody. This is in contrast to a significant rise in [Ca2+]i in H9 cells following similar stimulation. These data demonstrate abnormalities in the plasma membrane potential and [Ca2+]i levels in chronically infected T cells with HIV. These abnormalities in signal transduction of the T-cell activation pathway could be responsible for T-cell dysfunction in patients with HIV infection.
有充分证据表明，丝裂原/抗原激活T淋巴细胞伴随着细胞内游离钙（[Ca2+]i）升高、膜电位变化、肌醇磷脂代谢以及蛋白激酶C激活。这些信号转导的早期事件最终导致淋巴细胞激活的晚期事件，即DNA合成、淋巴因子产生和细胞增殖。在本研究中，我们检测了人类免疫缺陷病毒（HIV）对膜电位和[Ca2+]i水平变化的影响。与未感染的H9细胞系相比，感染HIV（H9/HTLV IIIb）的T细胞系膜电位显著降低（去极化），并且对植物血凝素（PHA）或抗T3（抗CD3）单克隆抗体无正常反应。与H9细胞相比，H9/HTLV IIIb细胞的基础[Ca2+]i水平升高；然而，用PHA或抗T3单克隆抗体激活后，H9/HTLV IIIb细胞中[Ca2+]i的进一步升高非常少。这与类似刺激后H9细胞中[Ca2+]i的显著升高形成对比。这些数据表明，HIV慢性感染的T细胞中质膜电位和[Ca2+]i水平存在异常。T细胞激活途径信号转导的这些异常可能是HIV感染患者T细胞功能障碍的原因。
