Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.
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.Here we used a nov...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2007-07-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC1920556?pdf=render |
| _version_ | 1818586434808840192 |
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| author | Michaela Lucas Axel Ulsenheimer Katja Pfafferot Malte H J Heeg Silvana Gaudieri Norbert Grüner Andri Rauch J Tilman Gerlach Maria-Christina Jung Reinhart Zachoval Gerd R Pape Winfried Schraut Teresa Santantonio Hans Nitschko Martin Obermeier Rodney Phillips Thomas J Scriba Nasser Semmo Cheryl Day Jonathan N Weber Sarah Fidler Robert Thimme Anita Haberstroh Thomas F Baumert Paul Klenerman Helmut M Diepolder |
| author_facet | Michaela Lucas Axel Ulsenheimer Katja Pfafferot Malte H J Heeg Silvana Gaudieri Norbert Grüner Andri Rauch J Tilman Gerlach Maria-Christina Jung Reinhart Zachoval Gerd R Pape Winfried Schraut Teresa Santantonio Hans Nitschko Martin Obermeier Rodney Phillips Thomas J Scriba Nasser Semmo Cheryl Day Jonathan N Weber Sarah Fidler Robert Thimme Anita Haberstroh Thomas F Baumert Paul Klenerman Helmut M Diepolder |
| author_sort | Michaela Lucas |
| collection | DOAJ |
| description | 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.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.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. |
| first_indexed | 2024-12-16T08:52:55Z |
| format | Article |
| id | doaj.art-fe9de6f7104e48649f8ee0bdaf5db9c0 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T08:52:55Z |
| publishDate | 2007-07-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-fe9de6f7104e48649f8ee0bdaf5db9c02022-12-21T22:37:22ZengPublic Library of Science (PLoS)PLoS ONE1932-62032007-07-0127e64910.1371/journal.pone.0000649Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection.Michaela LucasAxel UlsenheimerKatja PfafferotMalte H J HeegSilvana GaudieriNorbert GrünerAndri RauchJ Tilman GerlachMaria-Christina JungReinhart ZachovalGerd R PapeWinfried SchrautTeresa SantantonioHans NitschkoMartin ObermeierRodney PhillipsThomas J ScribaNasser SemmoCheryl DayJonathan N WeberSarah FidlerRobert ThimmeAnita HaberstrohThomas F BaumertPaul KlenermanHelmut M DiepolderCD4+ 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.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.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.http://europepmc.org/articles/PMC1920556?pdf=render |
| spellingShingle | Michaela Lucas Axel Ulsenheimer Katja Pfafferot Malte H J Heeg Silvana Gaudieri Norbert Grüner Andri Rauch J Tilman Gerlach Maria-Christina Jung Reinhart Zachoval Gerd R Pape Winfried Schraut Teresa Santantonio Hans Nitschko Martin Obermeier Rodney Phillips Thomas J Scriba Nasser Semmo Cheryl Day Jonathan N Weber Sarah Fidler Robert Thimme Anita Haberstroh Thomas F Baumert Paul Klenerman Helmut M Diepolder Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. PLoS ONE |
| title | Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. |
| title_full | Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. |
| title_fullStr | Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. |
| title_full_unstemmed | Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. |
| title_short | Tracking virus-specific CD4+ T cells during and after acute hepatitis C virus infection. |
| title_sort | tracking virus specific cd4 t cells during and after acute hepatitis c virus infection |
| url | http://europepmc.org/articles/PMC1920556?pdf=render |
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