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Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. 2007
Michaela Lucas, and
Axel Ulsenheimer, and
Katja Pfafferot, and
Malte H J Heeg, and
Silvana Gaudieri, and
Norbert Grüner, and
Andri Rauch, and
J Tilman Gerlach, and
Maria-Christina Jung, and
Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
Rodney Phillips, and
Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
Sarah Fidler, and
Robert Thimme, and
Anita Haberstroh, and
Thomas F Baumert, and
Paul Klenerman, and
Helmut M Diepolder
Peter Medawar Building for Pathogen Research, Nuffield Department of Clinical Medicine, University of Oxford, Oxford, United Kingdom; Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Perth, Australia.
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. RESULTS 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 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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Katja Pfafferot, and
Malte H J Heeg, and
Silvana Gaudieri, and
Norbert Grüner, and
Andri Rauch, and
J Tilman Gerlach, and
Maria-Christina Jung, and
Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
Rodney Phillips, and
Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
Sarah Fidler, and
Robert Thimme, and
Anita Haberstroh, and
Thomas F Baumert, and
Paul Klenerman, and
Helmut M Diepolder
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Norbert Grüner, and
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Reinhart Zachoval, and
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Winfried Schraut, and
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Hans Nitschko, and
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Nasser Semmo, and
Cheryl Day, and
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Andri Rauch, and
J Tilman Gerlach, and
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Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
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Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
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J Tilman Gerlach, and
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Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
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Thomas J Scriba, and
Nasser Semmo, and
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Jonathan N Weber, and
Sarah Fidler, and
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Paul Klenerman, and
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Katja Pfafferot, and
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Norbert Grüner, and
Andri Rauch, and
J Tilman Gerlach, and
Maria-Christina Jung, and
Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
Rodney Phillips, and
Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
Sarah Fidler, and
Robert Thimme, and
Anita Haberstroh, and
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Helmut M Diepolder
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Andri Rauch, and
J Tilman Gerlach, and
Maria-Christina Jung, and
Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
Rodney Phillips, and
Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
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Thomas F Baumert, and
Paul Klenerman, and
Helmut M Diepolder
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Journal of molecular medicine (Berlin, Germany),
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Malte H J Heeg, and
Silvana Gaudieri, and
Norbert Grüner, and
Andri Rauch, and
J Tilman Gerlach, and
Maria-Christina Jung, and
Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
Rodney Phillips, and
Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
Sarah Fidler, and
Robert Thimme, and
Anita Haberstroh, and
Thomas F Baumert, and
Paul Klenerman, and
Helmut M Diepolder
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Katja Pfafferot, and
Malte H J Heeg, and
Silvana Gaudieri, and
Norbert Grüner, and
Andri Rauch, and
J Tilman Gerlach, and
Maria-Christina Jung, and
Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
Rodney Phillips, and
Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
Sarah Fidler, and
Robert Thimme, and
Anita Haberstroh, and
Thomas F Baumert, and
Paul Klenerman, and
Helmut M Diepolder
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Axel Ulsenheimer, and
Katja Pfafferot, and
Malte H J Heeg, and
Silvana Gaudieri, and
Norbert Grüner, and
Andri Rauch, and
J Tilman Gerlach, and
Maria-Christina Jung, and
Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
Rodney Phillips, and
Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
Sarah Fidler, and
Robert Thimme, and
Anita Haberstroh, and
Thomas F Baumert, and
Paul Klenerman, and
Helmut M Diepolder
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Michaela Lucas, and
Axel Ulsenheimer, and
Katja Pfafferot, and
Malte H J Heeg, and
Silvana Gaudieri, and
Norbert Grüner, and
Andri Rauch, and
J Tilman Gerlach, and
Maria-Christina Jung, and
Reinhart Zachoval, and
Gerd R Pape, and
Winfried Schraut, and
Teresa Santantonio, and
Hans Nitschko, and
Martin Obermeier, and
Rodney Phillips, and
Thomas J Scriba, and
Nasser Semmo, and
Cheryl Day, and
Jonathan N Weber, and
Sarah Fidler, and
Robert Thimme, and
Anita Haberstroh, and
Thomas F Baumert, and
Paul Klenerman, and
Helmut M Diepolder
October 1999,
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