T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses

Saeidi, Alireza and Zandi, Keivan and Cheok, Yi Ying and Saeidi, Hamidreza and Wong, Won Fen and Lee, Chalystha Yie Qin and Cheong, Heng Choon and Yong, Yean Kong and Larsson, Marie and Shankar, Esaki Muthu (2018) T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses. Frontiers in Immunology, 9. 02569. ISSN 1664-3224, DOI https://doi.org/10.3389/fimmu.2018.02569.

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Official URL: https://doi.org/10.3389/fimmu.2018.02569

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.

Item Type: Article
Funders: UNSPECIFIED
Uncontrolled Keywords: Epigenetics; Immunotherapy; Metabolism; PD-1; Rejuvenation; T-bet; T-cell exhaustion
Subjects: R Medicine
Divisions: Faculty of Medicine
Centre of Excellence for Research in AIDS (CERiA)
Depositing User: Ms. Juhaida Abd Rahim
Date Deposited: 08 Apr 2019 06:37
Last Modified: 08 Apr 2019 06:37
URI: http://eprints.um.edu.my/id/eprint/20831

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