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

Publication

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

Journal Paper/Review - Oct 1, 2008

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

Citation

Ciuffreda D, Bernasconi E, Monnat M, Cerny A, Chuard C, Borovicka J, Mentha G, Pascual M, Gonvers J, Pantaleo G, Oneta C, Malinverni R, Comte D, Cavassini M, Giostra E, Buhler L, Perruchoud M, Heim M, Battegay M, Genné D, Mulhaupt B, Dutoit V. Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication. European journal of immunology 2008; 38:2665-77.

Type

Journal Paper/Review (English)

Journal

European journal of immunology 2008; 38

Publication Date

Oct 1, 2008

Issn Print

0014-2980

Pages

2665-77

Brief description/objective

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.