Gibellini D, Re M C, Ponti C, Maldini C, Celeghini C, Cappellini A, La Placa M, Zauli G
Microbiology Section, Department of Clinical and Experimental Medicine, University of Bologna, Via Massarenti 9, Bologna, 40138, Italy.
Cell Immunol. 2001 Feb 1;207(2):89-99. doi: 10.1006/cimm.2000.1746.
We have here investigated the effect of TNF-related apoptosis-inducing ligand (TRAIL), a new member of the TNF cytokine superfamily, on the survival of Jurkat lymphoblastoid cell lines stably transfected with plasmids expressing the wild-type or mutated (Cys22) human immunodeficiency virus type 1 (HIV-1) tat gene. Jurkat cells transfected with wild-type tat were resistant to TRAIL-mediated apoptosis, while Jurkat cells mock-transfected with the control plasmid or with a mutated nonfunctional tat cDNA were highly susceptible to TRAIL-mediated apoptosis. Also, pretreatment with low concentrations (10-100 ng/ml) of extracellular synthetic Tat protein partially protected Jurkat cells from TRAIL-mediated apoptosis. Taken together, these results demonstrated that endogenously expressed tat and, to a lesser extent, extracellular Tat block TRAIL-mediated apoptosis. Since it has been shown that primary lymphoid T cells purified from HIV-1-infected individuals are more susceptible than those purified from normal individuals to TRAIL-mediated apoptosis, our findings underscore a potentially important role of Tat in protecting HIV-1-infected cells from TRAIL-mediated apoptosis.
我们在此研究了肿瘤坏死因子相关凋亡诱导配体（TRAIL），肿瘤坏死因子细胞因子超家族的一个新成员，对稳定转染了表达野生型或突变型（Cys22）人类免疫缺陷病毒1型（HIV-1）tat基因质粒的Jurkat淋巴母细胞系存活的影响。转染野生型tat的Jurkat细胞对TRAIL介导的凋亡具有抗性，而用对照质粒或突变的无功能tat cDNA进行模拟转染的Jurkat细胞对TRAIL介导的凋亡高度敏感。此外，用低浓度（10 - 100 ng/ml）的细胞外合成Tat蛋白预处理可部分保护Jurkat细胞免受TRAIL介导的凋亡。综上所述，这些结果表明内源性表达的tat以及程度较轻的细胞外Tat可阻断TRAIL介导的凋亡。由于已经表明从HIV-1感染个体中纯化的原代淋巴细胞T比从正常个体中纯化的更易受TRAIL介导的凋亡影响，我们的发现强调了Tat在保护HIV-1感染细胞免受TRAIL介导的凋亡方面的潜在重要作用。
