Journal Article

Lack of full CD8 functional restoration after antiviral treatment for acute and chronic hepatitis C virus infection

Zerbini, Alessandro, Fasano, Massimo, Pilli, Massimo, Penna, Amalia, Ferrari, Carlo, Molinari, Atim, Ravanetti, Lara, Santantonio, Teresa, Orlandini, Alessandra, Barili, Valeria, Missale, Gabriele

2012

Overview

BackgroundHepatitis C virus (HCV) persistence is associated with impaired CD8 functions. Whether functional restoration of CD8 T cells chronically exposed to antigen can be obtained once the antigen is removed remains to be clarified.ObjectiveTo determine whether clearance of HCV by antiviral treatment can fully restore the antiviral function of HCV-specific CD8 cells.DesignPeripheral blood HCV-, Flu- and cytomegalovirus (CMV)-specific CD8 cells were quantified by tetramer staining in 28 patients whose HCV infection resolved after peginterferon or peginterferon/ribavirin treatment for either acute or chronic hepatitis and in eight subjects with acute HCV infection which resolved spontaneously for comparison. HCV-specific CD8 cells were evaluated for their phenotypic and functional characteristics by comparing different patient groups and CD8 cells with different viral specificities in the same patients.ResultsSustained viral response (SVR) did not lead to full maturation of a functional memory CD8 cell response. In particular, SVR in chronic infection was associated with a greater level of T cell dysfunction than responders after acute infection, who showed HCV-specific CD8 responses comparable to those of spontaneous resolvers but weaker than those of Flu-specific CD8 cells. Higher programmed death (PD)-1 expression was detected on HCV than on Flu- and CMV-specific CD8 cells and the effect of PD-1/PD-L1 blockade was better in SVRs after chronic than after acute HCV infection.ConclusionA better restoration of HCV-specific CD8 function was detectable after SVR in patients with acute hepatitis than in those with chronic disease. Thus, the difficulty in achieving a complete restoration of the antiviral T cell function should be considered in the design of immunomodulatory therapies.

• Publisher: BMJ Publishing Group Ltd and British Society of Gastroenterology,BMJ Publishing Group,BMJ Publishing Group LTD
• Subject: Antibiotics. Antiinfectious agents. Antiparasitic agents / Antigens / Antiviral agents / Antiviral Agents - pharmacology / Antiviral Agents - therapeutic use / Apoptosis / Apoptosis Regulatory Proteins - immunology / Apoptosis Regulatory Proteins - metabolism / Biological and medical sciences / CD8 antigen / CD8-Positive T-Lymphocytes - immunology / Chronic infection / Cytokines / Cytomegalovirus / Digestive tract / Female / Gastroenterology. Liver. Pancreas. Abdomen / Hepacivirus - drug effects / Hepacivirus - immunology / Hepatitis / hepatitis B / hepatitis C / Hepatitis C - drug therapy / Hepatitis C - immunology / Hepatitis C virus / Hepatitis C, Chronic - drug therapy / Hepatitis C, Chronic - immunology / Hepatitis C, Chronic - virology / Human viral diseases / Humans / Immunological memory / immunology in hepatology / Immunomodulation / Immunotherapy / Infections / infectious disease / Infectious diseases / Interferon / liver cirrhosis / Lymphocytes / Lymphocytes T / Male / Medical sciences / PD-1 protein / PD-L1 protein / Peptides / Peripheral blood / Pharmacology. Drug treatments / Programmed Cell Death 1 Receptor - metabolism / Recovery of function / Ribavirin / Ribavirin - pharmacology / Ribavirin - therapeutic use / Studies / T cell receptors / Viral diseases / Viral hepatitis / Viral infections / Viral Load - drug effects