title: Hepatitis C virus clearance correlates with HLA-DR expression on proliferating CD8+ T cells in immune-primed chimpanzees.
abstract: Vaccination of chimpanzees against hepatitis C virus (HCV) using T-cell-based vaccines targeting nonstructural proteins has not resulted in the same levels of control and clearance as those seen in animals reexposed after HCV clearance. We hypothesized that the outcome of infection depends on the different subtypes of activated T cells. We used multicolor flow cytometry to evaluate activation (CD38+/HLA-DR+) and proliferation (Ki67+/Bcl-2-low) profiles of CD4+ and CD8+ T cells in peripheral blood before and after challenge in chimpanzees vaccinated using DNA/adenovirus, mock-vaccinated, and chimpanzees that had spontaneously cleared infection (rechallenged). The frequencies of activated or proliferating CD8+ T cells peaked at 2 weeks postchallenge in the vaccinated and rechallenged animals, coinciding with reductions in viral titers. However, the magnitude of the responses did not correlate with outcome or sustained control of viral replication. In contrast, proliferation of the CD8+ T cells coexpressing HLA-DR either with or without CD38 expression was significantly higher at challenge in animals that rapidly cleared HCV and remained so throughout the follow-up period.
  
  
  CONCLUSIONS
  Our data suggest that the appearance of proliferating HLA-DR+/CD8+ T cells can be used as a predictor of a successfully primed memory immune response against HCV and as a marker of effective vaccination in clinical trials.
authors.affiliation: Laboratory of Hepatitis Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD.
authors.forename: Iryna
authors.initials: I
authors.lastname: Zubkova
authors.forename: Hongying
authors.initials: H
authors.lastname: Duan
authors.forename: Frances
authors.initials: F
authors.lastname: Wells
authors.forename: Howard
authors.initials: H
authors.lastname: Mostowski
authors.forename: Esther
authors.initials: E
authors.lastname: Chang
authors.forename: Kathleen
authors.initials: K
authors.lastname: Pirollo
authors.forename: Kris
authors.initials: K
authors.lastname: Krawczynski
authors.forename: Robert
authors.initials: R
authors.lastname: Lanford
authors.forename: Marian
authors.initials: M
authors.lastname: Major
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000276:immunology; D062705:Adenovirus Vaccines / Q000276:immunology; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000276:immunology*; D007156:Immunologic Memory / Q000276:immunology; D002679:Pan troglodytes / Q000276:immunology* / Q000821:virology*; D014761:Viral Hepatitis Vaccines / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
chemical_list: D062705:Adenovirus Vaccines; D006684:HLA-DR Antigens; D014761:Viral Hepatitis Vaccines; D051997:ADP-ribosyl Cyclase 1