Cai Hong-Jiao, Shi Jue, Yin Lin-Bo, Zheng Jie-Fu, Fu Ya-Jing, Jiang Yong-Jun, Shang Hong, Zhang Zi-Ning
NHC Key Laboratory of AIDS Immunology, National Clinical Research Center for Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, China.
Department of Central Laboratory, Dalian Municipal Central Hospital, Dalian, China.
Front Microbiol. 2022 Jul 6;13:880873. doi: 10.3389/fmicb.2022.880873. eCollection 2022.
Despite the benefits of antiretroviral therapy (ART) for people with HIV, T-cell dysfunction cannot be fully restored. Metabolic dysregulation is associated with dysfunction of HIV-1-specific T-cells. Exploration of the factors regulating metabolic fitness can help reverse T-cell dysfunction and provide new insights into the underlying mechanism.
In this study, HIV-infected individuals and HIV-negative control individuals (NCs) were enrolled. T-cell factor (TCF)1 expression in cells was determined by quantitative reverse-transcriptase polymerase chain reaction and flow cytometry. Relevant microarray data from the GEO database were analyzed to explore the underlying mechanism. The effects of TCF1 on T-cell function and metabolic function were assessed .
mRNA expression in peripheral blood mononuclear cells was downregulated in rapid progressors compared with long-term non-progressors individuals and NCs. TCF1 expression on CD4 and CD8 T-cells was downregulated in treatment-naïve HIV-infected individuals compared with NCs. Interleukin (IL)2 production and proliferative capacity were impaired in TCF1 knockdown T-cells. Moreover, glycolytic capacity and mitochondrial respiratory function were decreased in TCF1 knockdown T-cells, and depolarized mitochondria were increased in TCF1 knockdown T-cells.
Downregulation of TCF1 in HIV infection impairs T-cell proliferative capacity by disrupting mitochondrial function. These findings highlight the metabolic regulation as a pivotal mechanism of TCF1 in the regulation of T-cell dysfunction.
尽管抗逆转录病毒疗法（ART）对艾滋病毒感染者有益，但T细胞功能障碍无法完全恢复。代谢失调与HIV-1特异性T细胞功能障碍有关。探索调节代谢适应性的因素有助于逆转T细胞功能障碍，并为潜在机制提供新的见解。
在本研究中，纳入了HIV感染者和HIV阴性对照个体（NCs）。通过定量逆转录聚合酶链反应和流式细胞术测定细胞中T细胞因子（TCF）1的表达。分析来自GEO数据库的相关微阵列数据以探索潜在机制。评估TCF1对T细胞功能和代谢功能的影响。
与长期无进展个体和NCs相比，快速进展者外周血单个核细胞中的mRNA表达下调。与NCs相比，未经治疗的HIV感染个体的CD4和CD8 T细胞上的TCF1表达下调。TCF1敲低的T细胞中白细胞介素（IL）2的产生和增殖能力受损。此外，TCF1敲低的T细胞中糖酵解能力和线粒体呼吸功能降低，TCF1敲低的T细胞中去极化线粒体增加。
HIV感染中TCF1的下调通过破坏线粒体功能损害T细胞增殖能力。这些发现突出了代谢调节作为TCF1调节T细胞功能障碍的关键机制。
