CD8+ T cells of chronic HCV-infected patients express multiple negative immune checkpoints following stimulation with HCV peptides

• Published in: Cellular immunology Vol. 313; pp. 1 - 9
• Main Authors: Barathan, Muttiah, Mohamed, Rosmawati, Vadivelu, Jamuna, Chang, Li Yen, Vignesh, Ramachandran, Krishnan, Jayalakshmi, Sigamani, Panneer, Saeidi, Alireza, Ram, M. Ravishankar, Velu, Vijayakumar, Larsson, Marie, Shankar, Esaki M.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.03.2017
• Subjects: Adult; Aged; Aged, 80 and over; Antigens, Viral - immunology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Cells, Cultured; Co-inhibitory receptors; Costimulatory and Inhibitory T-Cell Receptors - genetics; Costimulatory and Inhibitory T-Cell Receptors - metabolism; Cytokines - metabolism; HCV; Hepacivirus - immunology; Hepatitis C, Chronic - immunology; Humans; Immune checkpoint; Immunosenescence; Inflammation Mediators - metabolism; Middle Aged; PD-1; Peptide Fragments - immunology; T-cell exhaustion; TIM-3; Viral Load; Young Adult; HCV; Immune checkpoint; T-cell exhaustion; Co-inhibitory receptors; TIM-3; PD-1
• ISSN: 0008-8749; 1090-2163; 1090-2163
• DOI: 10.1016/j.cellimm.2016.12.002

•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.