title: Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.
abstract: BACKGROUND
  CD4+ T cell help is critical in maintaining antiviral immune responses and such help has been shown to be sustained in acute resolving hepatitis C. In contrast, in evolving chronic hepatitis C CD4+ T cell helper responses appear to be absent or short-lived, using functional assays.
  
  
  RESULTS
  Here we used a novel HLA-DR1 tetramer containing a highly targeted CD4+ T cell epitope from the hepatitis C virus non-structural protein 4 to track number and phenotype of hepatitis C virus specific CD4+ T cells in a cohort of seven HLA-DR1 positive patients with acute hepatitis C in comparison to patients with chronic or resolved hepatitis C. We observed peptide-specific T cells in all seven patients with acute hepatitis C regardless of outcome at frequencies up to 0.65% of CD4+ T cells. Among patients who transiently controlled virus replication we observed loss of function, and/or physical deletion of tetramer+ CD4+ T cells before viral recrudescence. In some patients with chronic hepatitis C very low numbers of tetramer+ cells were detectable in peripheral blood, compared to robust responses detected in spontaneous resolvers. Importantly we did not observe escape mutations in this key CD4+ T cell epitope in patients with evolving chronic hepatitis C.
  
  
  CONCLUSIONS
  During acute hepatitis C a CD4+ T cell response against this epitope is readily induced in most, if not all, HLA-DR1+ patients. This antiviral T cell population becomes functionally impaired or is deleted early in the course of disease in those where viremia persists.
authors.affiliation: Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia.
authors.forename: Michaela
authors.initials: M
authors.lastname: Lucas
authors.forename: Axel
authors.initials: A
authors.lastname: Ulsenheimer
authors.forename: Katja
authors.initials: K
authors.lastname: Pfafferot
authors.forename: Malte H J
authors.initials: MH
authors.lastname: Heeg
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaudieri
authors.forename: Norbert
authors.initials: N
authors.lastname: Grüner
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: J Tilman
authors.initials: JT
authors.lastname: Gerlach
authors.forename: Maria-Christina
authors.initials: MC
authors.lastname: Jung
authors.forename: Reinhart
authors.initials: R
authors.lastname: Zachoval
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Pape
authors.forename: Winfried
authors.initials: W
authors.lastname: Schraut
authors.forename: Teresa
authors.initials: T
authors.lastname: Santantonio
authors.forename: Hans
authors.initials: H
authors.lastname: Nitschko
authors.forename: Martin
authors.initials: M
authors.lastname: Obermeier
authors.forename: Rodney
authors.initials: R
authors.lastname: Phillips
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Scriba
authors.forename: Nasser
authors.initials: N
authors.lastname: Semmo
authors.forename: Cheryl
authors.initials: C
authors.lastname: Day
authors.forename: Jonathan N
authors.initials: JN
authors.lastname: Weber
authors.forename: Sarah
authors.initials: S
authors.lastname: Fidler
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.forename: Anita
authors.initials: A
authors.lastname: Haberstroh
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Baumert
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Helmut M
authors.initials: HM
authors.lastname: Diepolder
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D017931:DNA Primers; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005838:Genotype; D015798:HLA-DR1 Antigen / Q000737:chemistry / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification*; D006526:Hepatitis C / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D008099:Liver / Q000276:immunology / Q000821:virology; D008297:Male; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D006377:T-Lymphocytes, Helper-Inducer / Q000821:virology*; D014764:Viral Proteins / Q000032:analysis / Q000737:chemistry / Q000276:immunology
chemical_list: D017931:DNA Primers; D018984:Epitopes, T-Lymphocyte; D015798:HLA-DR1 Antigen; D010446:Peptide Fragments; D014764:Viral Proteins