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. 2008 Oct;38(10):2665-77.
doi: 10.1002/eji.200838336.

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

Donatella Ciuffreda  1 , Denis Comte, Matthias Cavassini, Emiliano Giostra, Leo Bühler, Monika Perruchoud, Markus H Heim, Manuel Battegay, Daniel Genné, Beat Mulhaupt, Raffaele Malinverni, Carl Oneta, Enos Bernasconi, Martine Monnat, Andreas Cerny, Christian Chuard, Jan Borovicka, Gilles Mentha, Manuel Pascual, Jean-Jacques Gonvers, Giuseppe Pantaleo, Valérie Dutoit
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Free article

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

Donatella Ciuffreda et al. Eur J Immunol. 2008 Oct.
Free article

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.

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