Polyfunctional HCV-specific T-cell responses are associated with effective control of HCV replication.
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.
Ciuffreda
Donatella
D
Laboratory of AIDS Immunopathogenesis, Division of Immunology and Allergy, Department of Medicine, CHUV, Lausanne, Switzerland.
Comte
Denis
D
Cavassini
Matthias
M
Giostra
Emiliano
E
Bühler
Leo
L
Perruchoud
Monika
M
Heim
Markus H
MH
Battegay
Manuel
M
Genné
Daniel
D
Mulhaupt
Beat
B
Malinverni
Raffaele
R
Oneta
Carl
C
Bernasconi
Enos
E
Monnat
Martine
M
Cerny
Andreas
A
Chuard
Christian
C
Borovicka
Jan
J
Mentha
Gilles
G
Pascual
Manuel
M
Gonvers
Jean-Jacques
JJ
Pantaleo
Giuseppe
G
Dutoit
Valérie
V
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000821:virology; D016174:Hepacivirus / Q000276:immunology* / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology* / Q000821:virology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D016031:Liver Transplantation / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
D007376:Interleukin-2; D007371:Interferon-gamma