Overexpression of Fas antigen on T cells in advanced HIV-1 infection: differential ligation constantly induces apoptosis
Overexpression of Fas antigen on T cells in advanced HIV-1 infection: differential ligation constantly induces apoptosis
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晚期 HIV-1 感染中 T 细胞上 Fas 抗原过度表达：差异连接不断诱导细胞凋亡
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
F. Dammacco
中科院分区：
文献类型：
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作者：
F. Silvestris;P. Cafforio;M. Frassanito;M. Tucci;A. Romito;S. Nagata;F. Dammacco
目的：探讨HIV-1阳性患者不同疾病阶段外周血淋巴细胞Fas表达与凋亡程度的关系。设计：该研究包括分析Fas参与HIV-1感染过程中观察到的T细胞凋亡。由于Fas的连接可以导致共刺激的增殖或诱导未感染细胞的凋亡，我们评估了Fas激活的T细胞的效果，由不同特异性的单克隆抗体（MAb）从UB 2和CH 11克隆和激活的Fas配体（Fas-L）。方法：流式细胞仪检测Fas在外周血和植物血凝素（PHA）驱动的培养物来自59个HIV-1阳性的个人与不同的疾病控制和预防中心阶段。碘化丙啶细胞染色法检测凋亡细胞百分率。通过测量3 H-胸苷摄取的增殖试验，在来自患者和健康对照的外周T细胞中评估Fas连接的作用。结果：流式细胞仪分析显示，Fas主要表达在晚期疾病，虽然它是迅速暴露在PHA培养无症状的个人。在一些情况下，Fas过度表达与严重淋巴细胞减少患者细胞中大量亚二倍体DNA含量相关。增殖试验显示，来自UB 2克隆的免疫球蛋白（IG）G1 MAb在Fas连接后，显著抑制所有患者的T细胞中的3 H-胸苷摄取。这与对照中检测到的明显细胞活化和Fas阳性细胞系中观察到的弱抑制形成对比。此外，IgM抗Fas和重组Fas-L浓度诱导来自对照的新鲜T细胞的中度抑制强烈抑制来自患者的细胞的增殖速率。结论：我们的数据表明，Fas过度表达平行于疾病的进展，增加易感性的T细胞从HIV-1感染的个人进行凋亡可能包括Fas途径。在晚期HIV-1感染中功能衰竭的T细胞被引发凋亡，因为它们对Fas刺激的高敏感性，即使使用IgG 1 MAb，其对Fas的死亡结构域不反应。这表明Fas的敏感性增加与其三聚体连接无关，并支持Fas途径在疾病期间增加淋巴细胞凋亡中起作用的假设。
Objectives:To investigate Fas in peripheral lymphocytes from HIV-1-positive patients at different disease stages with respect to the extent of apoptosis. Design:The study included analysis of Fas involvement in T-cell apoptosis observed during HIV-1 infection. Because ligation of Fas can result in costimulation of proliferation or the induction of apoptosis in uninfected cells, we evaluated the effect on T cells of Fas activation by monoclonal antibodies (MAb) of different specificity from both UB2 and CH11 clones and activation by the Fas ligand (Fas-L). Methods:Fas was measured by FACS in peripheral blood and in phytohaemagglutinin (PHA)-driven cultures derived from 59 HIV-1-positive individuals with different Centers for Disease Control and Prevention stages. The percentage of apoptotic cells was detected by propidium iodide cell staining. The effect of Fas ligation was assessed in peripheral T cells from patients and healthy controls by a proliferative test measuring the 3H-thymidine uptake. Results:FACS analysis revealed that Fas was predominantly expressed in advanced disease, although it was promptly exposed in PHA cultures from asymptomatic individuals. In several instances, Fas overexpression was associated with substantial subdiploid DNA content in cells from severely lymphopenic patients. The proliferative assay showed a significant inhibition of 3H-thymidine uptake in T cells from all patients following Fas ligation by the immunoglobulin (Ig) G1 MAb from the UB2 clone. This was in contrast to the apparent cell activation detected in controls and the weak suppression observed in Fas-positive cell lines. In addition, the IgM anti-Fas and recombinant Fas-L concentrations inducing a moderate inhibition of fresh T cells from controls strongly depressed the proliferative rate of cells from patients. Conclusions:Our data suggest that Fas overexpression parallels the progression of the disease and that the increased susceptibility of T cells from HIV-1-infected individuals to undergo apoptosis may include a Fas pathway. Functionally exhausted T cells in advanced HIV-1 infection are primed to apoptosis because of their high sensitivity to Fas stimulation even using the IgG1 MAb, which is unreactive to the death domain of Fas. This suggests that the increased sensitivity of Fas is apparently unrelated to its trimeric ligation and supports the hypothesis that Fas pathway plays a role in increasing the lymphocyte apoptosis during the disease.