Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection

S. Bowyer; A. Ulsenheimer; M. Lucas; K. Pfafferott; M. Heeg; S. Gaudieri; N. Grüner; A. Rauch; J.T. Gerlach; M.C. Jung; R. Zachoval; G.R. Pape; W. Schraut; T. Santantonio; H. Nitschko; M. Obermeier; R. Phillips; T.J. Scriba; N. Semmo; C. Day; J.N. Weber; S. Fidler; R. Thimme; A. Haberstroh; T.F. Baumert; P. Klenerman; H.M. Diepolder

doi:10.1371/journal.pone.0000649

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Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection

Journal article

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Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection

S. Bowyer, A. Ulsenheimer, M. Lucas, K. Pfafferott, M. Heeg, S. Gaudieri, N. Grüner, A. Rauch, J.T. Gerlach, M.C. Jung, …

PLoS ONE, Vol.2(7), e649

2007

DOI: https://doi.org/10.1371/journal.pone.0000649

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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.

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Title: Tracking Virus-Specific CD4+ T Cells during and after Acute Hepatitis C Virus Infection
Authors/Creators: S. Bowyer (Author/Creator)
A. Ulsenheimer (Author/Creator) - Ludwig-Maximilians-Universität München
M. Lucas (Author/Creator) - Murdoch University
K. Pfafferott (Author/Creator)
M. Heeg (Author/Creator)
S. Gaudieri (Author/Creator) - Royal Perth Hospital
N. Grüner (Author/Creator) - Ludwig-Maximilians-Universität München
A. Rauch (Author/Creator) - Royal Perth Hospital
J.T. Gerlach (Author/Creator) - Ludwig-Maximilians-Universität München
M.C. Jung (Author/Creator) - Ludwig-Maximilians-Universität München
R. Zachoval (Author/Creator) - Ludwig-Maximilians-Universität München
G.R. Pape (Author/Creator) - Ludwig-Maximilians-Universität München
W. Schraut (Author/Creator) - Ludwig-Maximilians-Universität München
T. Santantonio (Author/Creator) - University of Bari Aldo Moro
H. Nitschko (Author/Creator) - Ludwig-Maximilians-Universität München
M. Obermeier (Author/Creator) - Ludwig-Maximilians-Universität München
R. Phillips (Author/Creator) - Medawar Building for Pathogen Research
T.J. Scriba (Author/Creator) - Medawar Building for Pathogen Research
N. Semmo (Author/Creator) - Medawar Building for Pathogen Research
C. Day (Author/Creator) - Medawar Building for Pathogen Research
J.N. Weber (Author/Creator) - St Mary's Hospital
S. Fidler (Author/Creator) - St Mary's Hospital
R. Thimme (Author/Creator) - University of Freiburg
A. Haberstroh (Author/Creator) - University of Freiburg
T.F. Baumert (Author/Creator) - Inserm
P. Klenerman (Author/Creator) - Medawar Building for Pathogen Research
H.M. Diepolder (Author/Creator) - Ludwig-Maximilians-Universität München
Publication Details: PLoS ONE, Vol.2(7), e649
Publisher: Public Library of Science
Identifiers: 991005542574907891
Copyright: © 2007 Lucas et al.
Murdoch Affiliation: Centre for Clinical Immunology and Biomedical Statistics
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.125 Hepatitis; 1.125.83 HCV
Web Of Science research areas: Immunology
ESI research areas: Immunology