CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides
•HCV peptide-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease.•HCV peptide-specific T cells of chronic HCV patients had significant increase of CTLA-4.•The levels of IL-2, IL-17A and IL-6 were decreased in the T cell cultures of chronic HCV patients.•Chronic HCV di...
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Published in | Cellular immunology Vol. 313; pp. 1 - 9 |
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Main Authors | , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Netherlands
Elsevier Inc
01.03.2017
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Subjects | |
Online Access | Get full text |
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Summary: | •HCV peptide-specific CD4+ and CD8+ T cells are key to successful viral clearance in HCV disease.•HCV peptide-specific T cells of chronic HCV patients had significant increase of CTLA-4.•The levels of IL-2, IL-17A and IL-6 were decreased in the T cell cultures of chronic HCV patients.•Chronic HCV disease results in functional T-cell exhaustion likely assisting viral persistence.
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™ 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-β1 were significantly increased, the levels of pro-inflammatory cytokines IL-2, TNF-α, 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0008-8749 1090-2163 1090-2163 |
DOI: | 10.1016/j.cellimm.2016.12.002 |