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-γ and IL-2 production and ability of CD4 and CD8 T cells to proliferate were assessed after stimulation with HCVderived 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-γ and single IFN-γ-producing CD4+ and dual IL-2/IFN-γ and single IFN-γ-producing CD81+ cells. In contrast, HCV-specific T-cell responses had an effector profile in HIV/HCV coinfected individuals and liver transplant recipients with absence of single IL-2-producing HCV-specific CD4+ and dual IL-2/IFN-γ-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 that immune-based mechanisms may contribute to explain the accelerated course of HCV infection in conditions of HIV-1 Co-infection and liver transplantation. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.