title: Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication.
abstract: HCV infection has a severe course of disease in HIV/HCV co-infection and in liver transplant recipients. However, the mechanisms involved remain unclear. Here, we evaluated functional profiles of HCV-specific T-cell responses in 86 HCV mono-infected patients, 48 HIV/HCV co-infected patients and 42 liver transplant recipients. IFN-gamma and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCV-derived peptides. We observed that HCV-specific T-cell responses were polyfunctional in HCV mono-infected patients, with presence of proliferating single IL-2-, dual IL-2/IFN-gamma and single IFN-gamma-producing CD4+ and dual IL-2/IFN-gamma and single IFN-gamma-producing CD8+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV co-infected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-gamma-producing CD8+ T cells. In addition, HCV-specific proliferation of CD4+ and CD8+ T cells was severely impaired in HIV/HCV co-infected patients and liver transplant recipients. Importantly, "only effector" T-cell responses were associated with significantly higher HCV viral load and more severe liver fibrosis scores. Therefore, the present results suggest that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 co-infection and liver transplantation.
authors.affiliation: Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, CHUV, Lausanne, Switzerland.
authors.forename: Donatella
authors.initials: D
authors.lastname: Ciuffreda
authors.forename: Denis
authors.initials: D
authors.lastname: Comte
authors.forename: Matthias
authors.initials: M
authors.lastname: Cavassini
authors.forename: Emiliano
authors.initials: E
authors.lastname: Giostra
authors.forename: Leo
authors.initials: L
authors.lastname: Bühler
authors.forename: Monika
authors.initials: M
authors.lastname: Perruchoud
authors.forename: Markus H
authors.initials: MH
authors.lastname: Heim
authors.forename: Manuel
authors.initials: M
authors.lastname: Battegay
authors.forename: Daniel
authors.initials: D
authors.lastname: Genné
authors.forename: Beat
authors.initials: B
authors.lastname: Mulhaupt
authors.forename: Raffaele
authors.initials: R
authors.lastname: Malinverni
authors.forename: Carl
authors.initials: C
authors.lastname: Oneta
authors.forename: Enos
authors.initials: E
authors.lastname: Bernasconi
authors.forename: Martine
authors.initials: M
authors.lastname: Monnat
authors.forename: Andreas
authors.initials: A
authors.lastname: Cerny
authors.forename: Christian
authors.initials: C
authors.lastname: Chuard
authors.forename: Jan
authors.initials: J
authors.lastname: Borovicka
authors.forename: Gilles
authors.initials: G
authors.lastname: Mentha
authors.forename: Manuel
authors.initials: M
authors.lastname: Pascual
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Gonvers
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pantaleo
authors.forename: Valérie
authors.initials: V
authors.lastname: Dutoit
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D007376:Interleukin-2; D007371:Interferon-gamma