NDLI: Hepatitis C virus clearance correlates with HLA-DR expression on proliferating CD8+ T cells in immune-primed chimpanzees.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Zubkova, Iryna Duan, Hongying Wells, Frances Mostowski, Howard Chang, Esther Pirollo, Kathleen Krawczynski, Kris Lanford, Robert Major, Marian
Description	Country affiliation: Moldova Author Affiliation: Zubkova I ( Laboratory of Hepatitis Viruses, Division of Viral Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD.)
Abstract	UNLABELLED: 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. CONCLUSION: 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.
File Format	HTM / HTML
ISSN	02709139
e-ISSN	15273350
DOI	10.1002/hep.26747
Journal	Hepatology
Issue Number	3
Volume Number	59
Language	English
Publisher	Wiley
Publisher Date	2014-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Hepatology Cd8-positive T-lymphocytes Immunology Hla-dr Antigens Hepatitis C Pan Troglodytes Virology Adenovirus Vaccines Animals Antigens, Cd38 Cytology Flow Cytometry Genetics Immunologic Memory Viral Hepatitis Vaccines Virus Replication Research Support, Non-u.s. Gov't Research Support, U.s. Gov't, Non-p.h.s.
Content Type	Text
Resource Type	Article
Subject	Hepatology

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