慢性感染中的T细胞耗竭：逆转疲劳状态并重新获得最佳保护

StephenW

Front Immunol. 2018 Nov 9;9:2569. doi: 10.3389/fimmu.2018.02569. eCollection 2018.
T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses.
Saeidi A1,2, Zandi K3, Cheok YY1, Saeidi H4, Wong WF1, Lee CYQ1, Cheong HC1, Yong YK2,5, Larsson M6, Shankar EM7.
Author information

1
    Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
2
    Center of Excellence for Research in AIDS, University of Malaya, Kuala Lumpur, Malaysia.
3
    Department of Pediatrics School of Medicine Emory University, Atlanta, GA, United States.
4
    Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Putra Malaysia, Selangor, Malaysia.
5
    Laboratory Center, Xiamen University Malaysia, Sepang, Malaysia.
6
    Division of Molecular Virology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
7
    Division of Infection Biology and Medical Microbiology, Department of Life Sciences, School of Life Sciences, Central University of Tamil Nadu, Thiruvarur, India.

Abstract

T-cell exhaustion is a phenomenon of dysfunction or physical elimination of antigen-specific T cells reported in human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections as well as cancer. Exhaustion appears to be often restricted to CD8+ T cells responses in the literature, although CD4+ T cells have also been reported to be functionally exhausted in certain chronic infections. Although our understanding of the molecular mechanisms associated with the transcriptional regulation of T-cell exhaustion is advancing, it is imperative to also explore the central mechanisms that control the altered expression patterns. Targeting metabolic dysfunctions with mitochondrion-targeted antioxidants are also expected to improve the antiviral functions of exhausted virus-specific CD8+ T cells. In addition, it is crucial to consider the contributions of mitochondrial biogenesis on T-cell exhaustion and how mitochondrial metabolism of T cells could be targeted whilst treating chronic viral infections. Here, we review the current understanding of cardinal features of T-cell exhaustion in chronic infections, and have attempted to focus on recent discoveries, potential strategies to reverse exhaustion and reinvigorate optimal protective immune responses in the host.
KEYWORDS:

PD-1; T-bet; T-cell exhaustion; epigenetics; immunotherapy; metabolism; rejuvenation

PMID:
    30473697
PMCID:
    PMC6237934
DOI:
    10.3389/fimmu.2018.02569

StephenW

前免疫。 2018年11月9日; 9：2569。 doi：10.3389 / fimmu.2018.02569。 eCollection 2018。
慢性感染中的T细胞耗竭：逆转疲劳状态并重新获得最佳保护性免疫应答。
Saeidi A1,2，Zandi K3，Cheok YY1，Saeidi H4，Wong WF1，Lee CYQ1，Cheong HC1，Yong YK2,5，Larsson M6，Shankar EM7。
作者信息

1
    马来西亚吉隆坡马来亚大学医学院医学微生物学系。
2
    马来西亚吉隆坡马来亚大学艾滋病研究中心。
3
    美国乔治亚州亚特兰大埃默里大学儿科学部。
4
    马来西亚雪兰莪州Putra大学医学与健康科学学院生物医学科学系。
五
    马来西亚厦门大学实验中心，马来西亚雪邦。
6
    瑞典林雪平林雪平大学临床与实验医学系分子病毒学系。
7
    印度Thiruvarur，泰米尔纳德邦中央大学生命科学学院生命科学系感染生物学和医学微生物学系。

抽象

T细胞衰竭是人类免疫缺陷病毒（HIV），乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）感染以及癌症中报道的抗原特异性T细胞功能障碍或物理消除的现象。尽管CD4 + T细胞在某些慢性感染中也被证实功能性疲惫，但是在文献中疲劳似乎经常局限于CD8 + T细胞应答。尽管我们对与T细胞衰竭的转录调节相关的分子机制的理解正在发展，但是还必须探索控制改变的表达模式的中心机制。用线粒体靶向抗氧化剂靶向代谢功能障碍也有望改善耗尽的病毒特异性CD8 + T细胞的抗病毒功能。此外，至关重要的是要考虑线粒体生物发生对T细胞衰竭的贡献以及如何在治疗慢性病毒感染的同时靶向T细胞的线粒体代谢。在这里，我们回顾了目前对慢性感染中T细胞衰竭的主要特征的理解，并试图关注最近的发现，逆转衰竭的潜在策略，并在宿主中重振最佳的保护性免疫反应。
关键词：

PD-1; T-赌注; T细胞衰竭;表观遗传学;免疫治疗;代谢;复兴

结论：
    30473697
PMCID：
    PMC6237934
DOI：
    10.3389 / fimmu.2018.02569

StephenW

https://www.frontiersin.org/arti ... mmu.2018.02569/full