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Pathogenesis and Immunity

Sustained Dysfunction of Antiviral CD8+ T Lymphocytes after Infection with Hepatitis C Virus

Norbert H. Gruener, Franziska Lechner, Maria-Christina Jung, Helmut Diepolder, Tilman Gerlach, Georg Lauer, Bruce Walker, John Sullivan, Rodney Phillips, Gerd R. Pape, Paul Klenerman
Norbert H. Gruener
Institute for Immunology, D-80336 Munich, and
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Franziska Lechner
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
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Maria-Christina Jung
Medical Department II, Klinikum Grosshadern, D-81366 Munich, Germany;
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Helmut Diepolder
Medical Department II, Klinikum Grosshadern, D-81366 Munich, Germany;
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Tilman Gerlach
Medical Department II, Klinikum Grosshadern, D-81366 Munich, Germany;
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Georg Lauer
Infectious Diseases Unit and AIDS Research Center, Massachussets General Hospital and Harvard Medical School, Boston, Massachusetts 02129; and
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Bruce Walker
Infectious Diseases Unit and AIDS Research Center, Massachussets General Hospital and Harvard Medical School, Boston, Massachusetts 02129; and
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John Sullivan
Australian Red Cross Blood Service, Sydney 2000, Australia
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Rodney Phillips
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
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Gerd R. Pape
Institute for Immunology, D-80336 Munich, and
Medical Department II, Klinikum Grosshadern, D-81366 Munich, Germany;
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Paul Klenerman
Nuffield Department of Clinical Medicine, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
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DOI: 10.1128/JVI.75.12.5550-5558.2001
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ABSTRACT

Hepatitis C virus (HCV) sets up persistent infection in the majority of those exposed. It is likely that, as with other persistent viral infections, the efficacy of T-lymphocyte responses influences long-term outcome. However, little is known about the functional capacity of HCV-specific T-lymphocyte responses induced after acute infection. We investigated this by using major histocompatibility complex class I-peptide tetrameric complexes (tetramers), which allow direct detection of specific CD8+T lymphocytes ex vivo, independently of function. Here we show that, early after infection, virus-specific CD8+ T lymphocytes detected with a panel of four such tetramers are abnormal in terms of their synthesis of antiviral cytokines and lytic activity. Furthermore, this phenotype is commonly maintained long term, since large sustained populations of HCV-specific CD8+ T lymphocytes were identified, which consistently had very poor antiviral cytokine responses as measured in vitro. Overall, HCV-specific CD8+T lymphocytes show reduced synthesis of tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) after stimulation with either mitogens or peptides, compared to responses to Epstein-Barr virus and/or cytomegalovirus. This behavior of antiviral CD8+ T lymphocytes induced after HCV infection may contribute to viral persistence through failure to effectively suppress viral replication.

  • Copyright © 2001 American Society for Microbiology
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Sustained Dysfunction of Antiviral CD8+ T Lymphocytes after Infection with Hepatitis C Virus
Norbert H. Gruener, Franziska Lechner, Maria-Christina Jung, Helmut Diepolder, Tilman Gerlach, Georg Lauer, Bruce Walker, John Sullivan, Rodney Phillips, Gerd R. Pape, Paul Klenerman
Journal of Virology Jun 2001, 75 (12) 5550-5558; DOI: 10.1128/JVI.75.12.5550-5558.2001

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Sustained Dysfunction of Antiviral CD8+ T Lymphocytes after Infection with Hepatitis C Virus
Norbert H. Gruener, Franziska Lechner, Maria-Christina Jung, Helmut Diepolder, Tilman Gerlach, Georg Lauer, Bruce Walker, John Sullivan, Rodney Phillips, Gerd R. Pape, Paul Klenerman
Journal of Virology Jun 2001, 75 (12) 5550-5558; DOI: 10.1128/JVI.75.12.5550-5558.2001
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KEYWORDS

CD8-Positive T-Lymphocytes
cytokines
hepacivirus
Hepatitis C

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