Chan Yee Teng, Cheong Heng Choon, Tang Ting Fang, Rajasuriar Reena, Cheng Kian-Kai, Looi Chung Yeng, Wong Won Fen, Kamarulzaman Adeeba
Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia.
Biomedicines. 2022 Nov 4;10(11):0. doi: 10.3390/biomedicines10112809.
The progressive decline of CD8 cytotoxic T cells in human immunodeficiency virus (HIV)-infected patients due to infection-triggered cell exhaustion and cell death is significantly correlated with disease severity and progression into the life-threatening acquired immunodeficiency syndrome (AIDS) stage. T cell exhaustion is a condition of cell dysfunction despite antigen engagement, characterized by augmented surface expression of immune checkpoint molecules such as programmed cell death protein 1 (PD-1), which suppress T cell receptor (TCR) signaling and negatively impact the proliferative and effector activities of T cells. T cell function is tightly modulated by cellular glucose metabolism, which produces adequate energy to support a robust reaction when battling pathogen infection. The transition of the T cells from an active to an exhausted state following pathogen persistence involves a drastic change in metabolic activity. This review highlights the interplay between immune checkpoint molecules and glucose metabolism that contributes to T cell exhaustion in the context of chronic HIV infection, which could deliver an insight into the rational design of a novel therapeutic strategy.
在人类免疫缺陷病毒（HIV）感染患者中，由于感染引发的细胞耗竭和细胞死亡导致CD8细胞毒性T细胞逐渐减少，这与疾病严重程度以及进展到危及生命的获得性免疫缺陷综合征（AIDS）阶段显著相关。T细胞耗竭是一种尽管抗原参与但细胞功能仍出现障碍的状态，其特征是免疫检查点分子如程序性细胞死亡蛋白1（PD-1）的表面表达增加，这些分子会抑制T细胞受体（TCR）信号传导，并对T细胞的增殖和效应活性产生负面影响。T细胞功能受到细胞葡萄糖代谢的严格调控，当对抗病原体感染时，葡萄糖代谢会产生足够的能量来支持强烈的反应。病原体持续存在后，T细胞从活跃状态转变为耗竭状态涉及代谢活动的剧烈变化。本综述强调了免疫检查点分子与葡萄糖代谢之间的相互作用，这种相互作用在慢性HIV感染的背景下导致T细胞耗竭，这可能为新型治疗策略的合理设计提供见解。
