Herbein G, Van Lint C, Lovett J L, Verdin E
The Picower Institute for Medical Research, Manhasset, New York 11030, USA.
J Virol. 1998 Jan;72(1):660-70. doi: 10.1128/JVI.72.1.660-670.1998.
Apoptosis is a main feature of AIDS pathogenesis and is thought to play a role in the progressive decrease of CD4+ T lymphocytes in infected individuals. To determine whether apoptosis occurs in infected and/or in uninfected peripheral blood T lymphocytes, we have used a recombinant human immunodeficiency virus type 1 (HIV-1) infectious clone expressing the green fluorescent protein (GFP). Using flow cytometry, we have determined the incidence of apoptosis by either terminal transferase dUTP nick end labeling or annexin-V assays in different cell subpopulations, i.e., in CD4+ or CD8+ T cells that were GFP positive or negative. After HIV-1 infection of purified peripheral blood lymphocytes, we observed that apoptosis occurred mostly in infected CD4+ peripheral blood lymphocytes. Remarkably, the presence of monocyte-derived macrophages in the culture increased dramatically the apoptosis of uninfected bystander T lymphocytes, while apoptosis in HIV-infected T lymphocytes was not changed. We therefore demonstrate that HIV-induced apoptosis results from at least two distinct mechanisms: (i) direct apoptosis in HIV-infected CD4+ T lymphocytes and (ii) indirect apoptosis in uninfected T cells mediated by antigen-presenting cells.
细胞凋亡是艾滋病发病机制的一个主要特征，被认为在受感染个体中CD4 + T淋巴细胞的逐渐减少中起作用。为了确定细胞凋亡是否发生在受感染和/或未受感染的外周血T淋巴细胞中，我们使用了一种表达绿色荧光蛋白（GFP）的重组人免疫缺陷病毒1型（HIV-1）感染性克隆。通过流式细胞术，我们通过末端转移酶dUTP缺口末端标记或膜联蛋白-V检测法确定了不同细胞亚群（即GFP阳性或阴性的CD4 +或CD8 + T细胞）中细胞凋亡的发生率。在纯化的外周血淋巴细胞感染HIV-1后，我们观察到细胞凋亡主要发生在受感染的CD4 +外周血淋巴细胞中。值得注意的是，培养物中单核细胞衍生的巨噬细胞的存在显著增加了未受感染的旁观者T淋巴细胞的细胞凋亡，而HIV感染的T淋巴细胞中的细胞凋亡没有改变。因此，我们证明HIV诱导的细胞凋亡至少由两种不同的机制引起：（i）HIV感染的CD4 + T淋巴细胞中的直接细胞凋亡和（ii）由抗原呈递细胞介导的未受感染T细胞中的间接细胞凋亡。
