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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
general
Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection
PLoS ONE, Volume 2, No. 7, Article e649, Year 2007
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Description
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/Prencipal 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. © 2007 Lucas et al.
Authors & Co-Authors
Pfafferot, Katja
Australia, Perth
Royal Perth Hospital
Gaudieri, S.
Australia, Perth
Royal Perth Hospital
Australia, Perth
The University of Western Australia
Rauch, Andri
Australia, Perth
Royal Perth Hospital
Switzerland, Bern
University Hospital Bern
Santantonio, Teresa Antonia
Italy, Bari
Università Degli Studi Di Bari Aldo Moro
Nitschko, Hans
Germany, Munich
Ludwig-maximilians-universität München
Obermeier, Martin
Germany, Munich
Ludwig-maximilians-universität München
Phillips, Rodney E.
United Kingdom, Oxford
University of Oxford
Scriba, Thomas J.
United Kingdom, Oxford
University of Oxford
Day, Cheryl Cheryl L.
United Kingdom, Oxford
University of Oxford
Weber, Jonathan N.
United Kingdom, London
Imperial College London
Fidler, Sarah J.
United Kingdom, London
Imperial College London
Thimme, Robert
Germany, Freiburg Im Breisgau
Universität Freiburg
Baumert, Thomas F.
France, Strasbourg
Université de Strasbourg
Klenerman, Paul
United Kingdom, Oxford
University of Oxford
Diepolder, Helmut Michael
Germany, Munich
Ludwig-maximilians-universität München
Statistics
Citations: 79
Authors: 15
Affiliations: 9
Identifiers
Doi:
10.1371/journal.pone.0000649
ISSN:
19326203
Research Areas
Infectious Diseases
Study Design
Cross Sectional Study
Cohort Study