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: