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Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication

Comte, Denis
Cavassini, Matthias
Perruchoud, Monika
Heim, Markus H.
Battegay, Manuel
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Published in European Journal of Immunology. 2008, vol. 38, no. 10, p. 2665-2677
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.
Keywords CD4-Positive T-Lymphocytes/*immunologyCD8-Positive T-Lymphocytes/*immunologyHIV/immunologyHIV Infections/complications/*immunology/virologyHepacivirus/*immunology/physiologyHepatitis C, Chronic/complications/*immunology/virologyHumansInterferon-gamma/immunology/metabolismInterleukin-2/immunology/metabolismLiver Transplantation/immunologyViral LoadVirus Replication
PMID: 18958874
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Research groups Cultures cellulaires et transplantations (519)
Hépatologie chirurgicale (327)
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CIUFFREDA, Donatella et al. Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication. In: European Journal of Immunology, 2008, vol. 38, n° 10, p. 2665-2677. doi: 10.1002/eji.200838336 https://archive-ouverte.unige.ch/unige:19092

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Deposited on : 2012-03-27

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