Acquired T-cell sensitivity to TRAIL mediated killing during HIV infection is regulated by CXCR4-gp120 interactions
Acquired T-cell sensitivity to TRAIL mediated killing during HIV infection is regulated by CXCR4-gp120 interactions
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DOI：
10.1097/01.aids.0000176212.16205.23
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发表时间：
2005-07-22
期刊：
影响因子：
3.8
通讯作者：
Badley, AD
中科院分区：
文献类型：
--
作者：
Lum, JJ;Schnepple, DJ;Badley, AD
背景资料：对由死亡受体的肿瘤坏死因子家族的连接诱导的细胞凋亡的敏感性部分地由死亡受体表达控制。尽管细胞活化增强Fas受体表达并诱导Fas敏感性，但这种细胞活化既不改变TRAIL受体表达也不诱导TRAIL敏感性。HIV感染的细胞获得对TRAIL诱导的死亡的敏感性，尽管实现这一点的机制尚不明确。目的：确定来自HIV感染患者的细胞获得对TRAIL介导的杀伤的敏感性的机制。设计：体外评估TRAIL受体表达和TRAIL敏感性。方法：用嗜T gp 120处理Jurkat T细胞、来自HIV阴性供体的外周血淋巴细胞或表达CD 4、CXCR 4或CCR 5的人成骨血清瘤（HOS）细胞，M嗜性gp 120，或抗CD 4、CXCR 4或CCR 5的激动性抗体。TRAIL受体测定流式细胞术或逆转录-PCR和TRAIL的敏感性进行了评估，然后通过与重组TRAIL孵育膜联蛋白V荧光素异硫氰酸盐/碘化丙啶（PI）staining.Results：治疗未感染的Jurkat T细胞，以及与gp 120的原代T细胞的结果在上调的TRAIL死亡受体的表达和获得的敏感性TRAIL介导的细胞死亡。TRAIL死亡受体的表达和获得的TRAIL敏感性的增加需要趋化因子辅助受体CXCR 4，但不是CCR 5或CD 4 receptor.Conclusions：这些结果表明，趋化因子受体相互作用调节TRAIL受体的表达，并提供了一个解释获得的T细胞敏感性TRAIL介导的杀伤死亡在HIV感染。(c)2005年利平科特威廉姆斯&威尔金斯。
Background: Sensitivity towards apoptosis induced by ligation of the tumor necrosis factor family of death receptors is controlled in part by death receptor expression. Whereas cellular activation enhances Fas receptor expression and induces Fas sensitivity, such cellular activation neither alters TRAIL receptor expression nor induces TRAIL sensitivity. Cells infected by HIV acquire sensitivity to TRAIL induced death, although the mechanisms by which this is achieved are undefined.Objective: To define the mechanism by which cells from HIV infected patients acquire sensitivity to TRAIL mediated killing.Design: In vitro assessment of TRAIL receptor expression and TRAIL sensitivity.Methods: Treatment of Jurkat T cells, peripheral blood lymphocytes from HIV negative donors, or human osteogenic seroma (HOS) cells expressing CD4, CXCR4 or CCR5 with T tropic gp120, M tropic gp120, or agonistic antibodies against CD4, CXCR4 or CCR5. TRAIL receptors were measured by flow cytometry or reverse transcription-PCR and TRAIL sensitivity was assessed by incubation with recombinant TRAIL followed by Annexin V fluorescein isothiocyanate/Propidium Iodide (PI) staining.Results: Treatment of uninfected Jurkat T cells, as well as primary T cells with gp120 results in the upregulation of TRAIL death receptor expression and acquired sensitivity to TRAIL mediated cell death. The increase in TRAIL death receptor expression and acquisition of TRAIL sensitivity requires the chemokine coreceptor CXCR4 but not CCR5 or the CD4 receptor.Conclusions: These results indicate that chemokine receptor interactions regulate TRAIL receptor expression and provide an explanation for the acquired T cell sensitivity to TRAIL mediated killing death during HIV infection. (c) 2005 Lippincott Williams & Wilkins.