Tracking virus-specific CD4+T Cells during and after acute hepatitis C virus infection

Title: Tracking virus-specific CD4+T Cells during and after acute hepatitis C virus infection
Authors: Lucas, M
Ulsenheimer, A
Pfafferot, K
Heeg, MHJ
Gaudieri, S
Gruener, N
Rauch, A
Gerlach, JT
Jung, M-C
Zachoval, R
Pape, GR
Schraut, W
Santantonio, T
Nitschko, H
Obermeier, M
Phillips, R
Scriba, TJ
Semmo, N
Day, C
Weber, JN
Fidler, S
Thimme, R
Haberstroh, A
Baumert, TF
Klenerman, P
Diepolder, HM
Item Type: Journal Article
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. Methodology/Principal Findings. 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/Significance. 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.
Issue Date: 25-Jul-2007
Date of Acceptance: 18-Jun-2007
URI: http://hdl.handle.net/10044/1/50820
DOI: https://dx.doi.org/10.1371/journal.pone.0000649
ISSN: 1932-6203
Publisher: Public Library of Science
Journal / Book Title: PLOS One
Volume: 2
Issue: 7
Copyright Statement: © 2007 Lucas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MULTIDISCIPLINARY SCIENCES
Acute Disease
Amino Acid Sequence
Base Sequence
CD4-Positive T-Lymphocytes
DNA Primers
Epitopes, T-Lymphocyte
Female
Genotype
HLA-DR1 Antigen
Hepacivirus
Hepatitis C
Humans
Immunity, Cellular
Liver
Male
Peptide Fragments
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes, Helper-Inducer
Viral Proteins
MD Multidisciplinary
General Science & Technology
Publication Status: Published
Article Number: ARTN e649
Appears in Collections:Department of Medicine
Faculty of Medicine



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