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T-Cell Exhaustion in Chronic Infections: Reversing the State of Exhaustion and Reinvigorating Optimal Protective Immune Responses
Univ Malaya, Malaysia.
Emory Univ, GA USA.
Univ Malaya, Malaysia.
Univ Putra Malaysia, Malaysia.
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2018 (English)In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 9, article id 2569Article, review/survey (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2018. Vol. 9, article id 2569
Keywords [en]
T-cell exhaustion; PD-1; immunotherapy; rejuvenation; T-bet; metabolism; epigenetics
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-152802DOI: 10.3389/fimmu.2018.02569ISI: 000449653000001OAI: oai:DiVA.org:liu-152802DiVA, id: diva2:1265298
Note

Funding Agencies|Universiti Malaya Research Grant [RP021A-13HTM]

Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2019-03-22

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Citation style
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