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

Ciuffreda, D. and Comte, D. and Cavassini, M. and Giostra, E. and Bühler, L. and Perruchoud, M. and Heim, M. H. and Battegay, M. and Genné, D. and Mulhaupt, B. and Malinverni, R. and Oneta, C. and Bernasconi, E. and Monnat, M. and Cerny, A. and Chuard, C. and Borovicka, J. and Mentha, G. and Pascual, M. and Gonvers, J. J. and Pantaleo, G. and Dutoit, V.. (2008) Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication. European Journal of Immunology, Vol. 38, H. 10. pp. 2665-2677.

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Official URL: http://edoc.unibas.ch/dok/A6007135

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Infection Biology (Khanna)
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Hepatology Laboratory (Heim)
UniBasel Contributors:Battegay, Manuel E. and Heim, Markus H.
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:Verl. Chemie
ISSN:0014-2980
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:18

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