title: Hepatitis C-specific effector and regulatory CD4 T-cell responses are associated with the outcomes of primary infection.
abstract: Clearance of primary hepatitis C virus (HCV) infection has been associated with strong and broadly targeted cellular immune responses. This study aimed to characterize HCV-specific CD4+ effector and regulatory T-cell numbers and cytokine production during primary infection. Antigen-specific CD4+ T-cell responses were investigated in a longitudinal cohort of subjects from pre-infection to postoutcome, including subjects who cleared [n=12] or became chronically infected [n=17]. A cross-sectional cohort with previously cleared, or chronic infection [n=15 for each], was also studied. Peripheral blood mononuclear cells were incubated with HCV antigens and surface stained for T-effector (CD4+CD25highCD134+CD39-) and T-regulatory (CD4+CD25highCD134+CD39+) markers, and culture supernatants assayed for cytokine production. Contrary to expectations, the breadth and magnitude of the HCV-specific CD4+ T-cell responses were higher in subjects who became chronically infected. Subjects who cleared the virus had HCV-specific CD4+ T-cell responses dominated by effector T cells and produced higher levels of IFN-γ, in contrast to HCV-specific CD4+ T-cell responses dominated by regulatory T cells and more IL-10 production in those who became chronically infected. Better understanding of the role of antigen-specific CD4+ T-cell responses in primary HCV will further define pathogenesis and help guide development of a preventative vaccine.
authors: UNSW Australia, Kirby Institute (Viral Immunology Systems Program, VISP) and School of Medical Sciences (SOMS), Kensington, NSW, Australia.
authors: E
authors: E
authors: Keoshkerian
authors: UNSW Australia, SOMS (Infection and Immunology Research Centre, IIRC), Kensington, NSW, Australia.
authors: M
authors: M
authors: Hunter
authors: UNSW Australia, SOMS (Infection and Immunology Research Centre, IIRC), Kensington, NSW, Australia.
authors: B
authors: B
authors: Cameron
authors: UNSW Australia, SOMS (Infection and Immunology Research Centre, IIRC), Kensington, NSW, Australia.
authors: N
authors: N
authors: Nguyen
authors: UNSW Australia, SOMS (Infection and Immunology Research Centre, IIRC), Kensington, NSW, Australia.
authors: P
authors: P
authors: Sugden
authors: UNSW Australia, Kirby Institute (Viral Immunology Systems Program, VISP) and School of Medical Sciences (SOMS), Kensington, NSW, Australia.
authors: R
authors: R
authors: Bull
authors: UNSW Australia, St George and Sutherland Clinical School, Sydney, NSW, Australia.
authors: A
authors: A
authors: Zekry
authors: UNSW Australia, Kirby Institute (Viral Hepatitis Epidemiology and Prevention Program VHEPP), Kensington, NSW, Australia.
authors: L
authors: L
authors: Maher
authors: The Vaccine Research Institute (VRI), INSERM, Créteil, France.
authors: N
authors: N
authors: Seddiki
authors: UNSW Australia, Kirby Institute (Immunovirology and Pathogenesis Program, IVPP), Kensington, NSW, Australia.
authors: J
authors: J
authors: Zaunders
authors: UNSW Australia, Kirby Institute (Immunovirology and Pathogenesis Program, IVPP), Kensington, NSW, Australia.
authors: A
authors: A
authors: Kelleher
authors: UNSW Australia, Kirby Institute (Viral Immunology Systems Program, VISP) and School of Medical Sciences (SOMS), Kensington, NSW, Australia.
authors: A R
authors: AR
authors: Lloyd
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D005260:Female; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D016896:Treatment Outcome
chemical_list: D016207:Cytokines
keywords: T effectors; T regulatory cells; acute hepatitis C; antigen-specific CD4 T cells; cytokines