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Author Notes:

Correspondence: Esaki Muthu Shankar shankarem@cutn.ac.in

All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Subject:

Research Funding:

The work has also been funded by the Universiti Malaya Research Grant No. RP021A-13HTM to AS.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • T-cell exhaustion
  • PD-1
  • immunotherapy
  • rejuvenation
  • T-bet
  • metabolism
  • epigenetics
  • CHRONIC VIRAL-INFECTION
  • INHIBITORY RECEPTOR PD-1
  • C VIRUS-INFECTION
  • CHRONIC HEPATITIS-B
  • HIV-INFECTION
  • INFILTRATING LYMPHOCYTES
  • METABOLIC-REGULATION
  • CUTTING EDGE
  • IN-VIVO
  • EXPRESSION

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

Tools:

Journal Title:

Frontiers in Immunology

Volume:

Volume 9, Number NOV

Publisher:

, Pages 2569-2569

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

Copyright © 2018 Saeidi, Zandi, Cheok, Saeidi, Wong, Lee, Cheong, Yong, Larsson and Shankar.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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