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CD8+T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides
University of Malaya, Malaysia.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
University of Malaya, Malaysia.
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2017 (English)In: Cellular Immunology, ISSN 0008-8749, E-ISSN 1090-2163, Vol. 313Article in journal (Refereed) Published
Abstract [en]

Hepatitis C virus (HCV)-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease. Accumulation of exhausted HCV-specific T cells during chronic infection results in considerable loss of protective functional immune responses. The role of T-cell exhaustion in chronic HCV disease remains poorly understood. Here, we studied the frequency of HCV peptide-stimulated T cells expressing negative immune checkpoints (PD-1, CTLA-4, TRAIL, TIM-3 and BTLA) by flow cytometry, and measured the levels of Th1/Th2/Th17 cytokines secreted by T cells by a commercial Multi-Analyte ELISArray (TM) following in vitro stimulation of T cells using HCV peptides and phytohemagglutinin (PHA). HCV peptide stimulated CD4+ and CD8+ T cells of chronic HCV (CHC) patients showed significant increase of CTLA-4. Furthermore, HCV peptide-stimulated CD4+ T cells of CHC patients also displayed relatively higher levels of PD-1 and TRAIL, whereas TIM-3 was up-regulated on HCV peptide-stimulated CD8+ T cells. Whereas the levels of IL-10 and TGF-beta 1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-alpha, IL-17A and IL-6 were markedly decreased in the T cell cultures of CHC patients. Chronic HCV infection results in functional exhaustion of CD4+ and CD8+ T cells likely contributing to viral persistence. (C) 2016 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
ACADEMIC PRESS INC ELSEVIER SCIENCE , 2017. Vol. 313
Keyword [en]
Co-inhibitory receptors; HCV; Immune checkpoint; PD-1; TIM-3; T-cell exhaustion
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-136652DOI: 10.1016/j.cellimm.2016.12.002ISI: 000396185500001PubMedID: 28104239OAI: oai:DiVA.org:liu-136652DiVA: diva2:1089831
Note

Funding Agencies|High Impact Research (HIR), University of Malaya [UM.C.625/1/HIR/139]; University of Malaya Post Graduate Research Grant (PPP) [PG118-2014A]; University of Malaya Fellowship Scheme; Swedish Research Council; Swedish Physicians against AIDS Research Foundation; Swedish-International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine; [AI52731]

Available from: 2017-04-21 Created: 2017-04-21 Last updated: 2017-04-21

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Larsson, Marie
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CiteExportLink to record
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Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
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More styles
Language
  • de-DE
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  • Other locale
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