title: Lack of full CD8 functional restoration after antiviral treatment for acute and chronic hepatitis C virus infection.
abstract: BACKGROUND
  Hepatitis 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.
  
  
  OBJECTIVE
  To determine whether clearance of HCV by antiviral treatment can fully restore the antiviral function of HCV-specific CD8 cells.
  
  
  METHODS
  Peripheral 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.
  
  
  RESULTS
  Sustained 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.
  
  
  CONCLUSIONS
  A 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.
authors.affiliation: Laboratory of Viral Immunopathology, Unit of Infectious Diseases and Hepatology, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy. missale@tin.it
authors.forename: Gabriele
authors.initials: G
authors.lastname: Missale
authors.forename: Massimo
authors.initials: M
authors.lastname: Pilli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Zerbini
authors.forename: Amalia
authors.initials: A
authors.lastname: Penna
authors.forename: Lara
authors.initials: L
authors.lastname: Ravanetti
authors.forename: Valeria
authors.initials: V
authors.lastname: Barili
authors.forename: Alessandra
authors.initials: A
authors.lastname: Orlandini
authors.forename: Atim
authors.initials: A
authors.lastname: Molinari
authors.forename: Massimo
authors.initials: M
authors.lastname: Fasano
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.forename: Carlo
authors.initials: C
authors.lastname: Ferrari
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology* / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D005260:Female; D016174:Hepacivirus / Q000187:drug effects* / Q000276:immunology; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000188:drug therapy / Q000276:immunology / Q000821:virology; D006801:Humans; D008297:Male; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D012254:Ribavirin / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D051017:Apoptosis Regulatory Proteins; D061026:Programmed Cell Death 1 Receptor; D012254:Ribavirin