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对接受联合抗逆转录病毒治疗的病毒学抑制的HIV阳性个体的CD4+和CD8+ T细胞中的代谢和线粒体动力学进行评估。

Assessment of metabolic and mitochondrial dynamics in CD4+ and CD8+ T cells in virologically suppressed HIV-positive individuals on combination antiretroviral therapy.

作者信息

Masson Jesse J R, Murphy Andrew J, Lee Man K S, Ostrowski Matias, Crowe Suzanne M, Palmer Clovis S

机构信息

James Cook University, Cairns, Australia.

Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.

出版信息

PLoS One. 2017 Aug 30;12(8):e0183931. doi: 10.1371/journal.pone.0183931. eCollection 2017.

Abstract

Metabolism plays a fundamental role in supporting the growth, proliferation and effector functions of T cells. We investigated the impact of HIV infection on key processes that regulate glucose uptake and mitochondrial biogenesis in subpopulations of CD4+ and CD8+ T cells from 18 virologically-suppressed HIV-positive individuals on combination antiretroviral therapy (cART; median CD4+ cell count: 728 cells/μl) and 13 HIV seronegative controls. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production were also analysed in total CD4+ and CD8+ T cells. Among HIV+/cART individuals, expression of glucose transporter (Glut1) and mitochondrial density were highest within central memory and naïve CD4+ T cells, and lowest among effector memory and transitional memory T cells, with similar trends in HIV-negative controls. Compared to HIV-negative controls, there was a trend towards higher percentage of circulating CD4+Glut1+ T cells in HIV+/cART participants. There were no significant differences in mitochondrial dynamics between subject groups. Glut1 expression was positively correlated with mitochondrial density and MMP in total CD4+ T cells, while MMP was also positively correlated with ROS production in both CD4+ and CD8+ T cells. Our study characterizes specific metabolic features of CD4+ and CD8+ T cells in HIV-negative and HIV+/cART individuals and will invite future studies to explore the immunometabolic consequences of HIV infection.

摘要

代谢在支持T细胞的生长、增殖和效应功能方面发挥着重要作用。我们研究了HIV感染对18名接受联合抗逆转录病毒治疗(cART;CD4+细胞计数中位数:728个/μl)且病毒学抑制的HIV阳性个体以及13名HIV血清阴性对照者的CD4+和CD8+T细胞亚群中调节葡萄糖摄取和线粒体生物合成的关键过程的影响。还对总CD4+和CD8+T细胞中的线粒体膜电位(MMP)和活性氧(ROS)生成进行了分析。在HIV+/cART个体中,葡萄糖转运蛋白(Glut1)的表达和线粒体密度在中枢记忆和初始CD4+T细胞中最高,而在效应记忆和过渡记忆T细胞中最低,HIV阴性对照者也有类似趋势。与HIV阴性对照者相比,HIV+/cART参与者中循环CD4+Glut1+T细胞的百分比有升高趋势。各受试者组之间的线粒体动力学无显著差异。在总CD4+T细胞中,Glut1表达与线粒体密度和MMP呈正相关,而在CD4+和CD8+T细胞中,MMP也与ROS生成呈正相关。我们的研究描述了HIV阴性和HIV+/cART个体中CD4+和CD8+T细胞的特定代谢特征,并将促使未来的研究探索HIV感染的免疫代谢后果。

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