Accelerated apoptosis in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus type-1 infected patients and in CD4 cross-linked PBMCs from normal individuals.
Accelerated apoptosis in peripheral blood mononuclear cells (PBMCs) from human immunodeficiency virus type-1 infected patients and in CD4 cross-linked PBMCs from normal individuals.
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DOI：
10.1182/blood.v82.11.3392.bloodjournal82113392
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发表时间：
1993-12
期刊：
影响因子：
20.3
通讯作者：
N. Oyaizu;T. McCloskey;Maria Coronesi;N. Chirmule;V. Kalyanaraman;S. Pahwa
中科院分区：
文献类型：
--
作者：
N. Oyaizu;T. McCloskey;Maria Coronesi;N. Chirmule;V. Kalyanaraman;S. Pahwa
本研究探讨了细胞凋亡作为人类免疫缺陷病毒1型（HIV-1）感染中CD 4 + T细胞耗竭的机制。虽然最近的几项研究表明，HIV感染者的T细胞对细胞凋亡的敏感性增强，但细胞凋亡的机制在很大程度上是未知的。通过使用流式细胞术技术和形态学，我们已经定量的百分比进行细胞凋亡的外周血单核细胞（PBMC）从HIV血清阴性的捐助者和HIV感染的无症状患者。PBMC在没有任何刺激的情况下或与大肠杆菌肠毒素B、抗T细胞受体（TCR）α β单克隆抗体WT-31或植物血凝素一起培养长达6天。此外，我们试图确定是否交联的CD 4随后在体外的TCR刺激的各种模式可以诱导正常PBMC的凋亡。在这里，我们表明：（1）患者PMBCs进行显着的自发性凋亡;（2）刺激T细胞的患者以及正常供体的结果在增加凋亡;和（3）交联的CD 4分子是足以诱导凋亡的CD 4 + T细胞，如果交联是在未分级的PBMC中进行，但如果CD 4分子交联的纯化的T细胞制剂。这些观察结果强烈表明，通过细胞凋亡加速细胞死亡在HIV-1感染的发病机制中起着重要作用。同时，我们的观察结果表明，体内CD 4的交联是HIV感染中加速细胞死亡机制的主要贡献者。
This study investigates apoptosis as a mechanism for CD4+ T-cell depletion in human immunodeficiency virus type-1 (HIV-1) infection. Although several recent studies have shown that T cells of HIV-infected individuals show enhanced susceptibility to cell death by apoptosis, the mechanisms responsible for apoptosis are largely unknown. By using a flow cytometric technique and by morphology, we have quantitated the percentage of cells undergoing apoptosis in peripheral blood mononuclear cells (PBMCs) from HIV-seronegative donors and from HIV-infected asymptomatic patients. The PBMCs were cultured without any stimulus or with staphylococcus enterotoxin B, anti-T-cell receptor (TCR) alpha beta monoclonal antibody WT-31, or phytohemagglutinin for periods up to 6 days. In addition, we sought to determine whether cross-linking of CD4 followed by various modes of TCR stimulation in vitro could induce apoptosis in normal PBMCs. Here we show that (1) patient PMBCs undergo marked spontaneous apoptosis; (2) stimulation of T cells of patients as well as normal donors results in increased apoptosis; and (3) cross-linking of CD4 molecules is sufficient to induce apoptosis in CD4+ T cells if cross-linking is performed in unfractioned PBMCs, but not if CD4 molecules are cross-linked in purified T-cell preparations. These observations strongly suggest that accelerated cell death through apoptosis plays an important role in the pathogenesis of HIV-1 infection. At the same time, our observations implicate cross-linking of CD4 in vivo as a major contributor to this mechanism of accelerated cell death in HIV infection.