title: Functional dichotomy of Vδ2 γδ T cells in chronic hepatitis C virus infections: role in cytotoxicity but not for IFN-γ production.
abstract: Vδ2 γδ (Vδ2) T cells, a major human γδ T cell subset, exhibit broad anti-tumor and anti-infective activity; however, their precise role in chronic hepatitis C virus (HCV) infections remains unclear. In this study, we analyzed the phenotype and function of Vδ2 T cells in 43 HCV-infected patients compared to 39 healthy controls (HCs). Vδ2 T cells from HCV-infected patients were activated and differentiated into effector cells. Vδ2 T cells in patients expressed significantly higher levels of natural killer (NK) cell markers CD56 and CD16 than in HCs, acquiring cytotoxic NK-like phenotype. The Vδ2 T cell phenotype was associated with increased cytolytic effector molecules expression in HCV-infected patients with elevated serum ALT levels. Surprisingly, Vδ2 T cells in patients had a markedly impaired capacity to produce IFN-γ. Further in vitro and in vivo analysis showed that interferon-α, which was induced during HCV infection, caused Vδ2 T cell function bias toward cytotoxicity. These results suggest a functional dichotomy for Vδ2 T cells in chronic HCV infections: a role in cytotoxicity but not for IFN-γ production, which may contribute to both the liver inflammation and HCV persistence.
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Wenwei
authors.initials: W
authors.lastname: Yin
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Shiwen
authors.initials: S
authors.lastname: Tong
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Qiongfang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Jianying
authors.initials: J
authors.lastname: Shao
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Peng
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Huaidong
authors.initials: H
authors.lastname: Hu
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Peng
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Institute of Immunology, School of Life Sciences, University of Science and Technology of China, Hefei, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Tian
authors.affiliation: Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, Department of Infectious Diseases, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, P. R. China.
authors.forename: Dazhi
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D016022:Case-Control Studies; D003602:Cytotoxicity, Immunologic; D005260:Female; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis*; D000075942:Intraepithelial Lymphocytes / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D008875:Middle Aged
chemical_list: D016898:Interferon-alpha; D007371:Interferon-gamma; D000410:Alanine Transaminase