Cell-mediated cytotoxicity in hepatitis A virus infection

Authors

  • Dr. Angelika Vallbracht,

    Corresponding author
    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
    • Department of Medical Virology, Hygiene-Institute, University of Tübingen. Silcherstr. 7, D-7400 Tubingen, Federal Republic of Germany
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  • Peter Gabriel,

    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
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  • Katharina Maier,

    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
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  • Franz Hartmann,

    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
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  • Hans Jörg Steinhardt,

    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
    Current affiliation:
    1. Medizinische Universitätsklinik und Poliklinik, D-65 Mainz, Federal Republic of Germany
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  • Claudia Müller,

    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
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  • Alexis Wolf,

    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
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  • Klaus Herbert Manncke,

    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
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  • Bertram Flehmig

    1. Department of Medical Virology, Hygiene-Institute, University of Tubingen, D-74 Tübingen, Federal Republic of Germany
    2. Departments of Internal Medicine and Surgery, University of Tubingen, D-74 Tubingen, Federal Republic of Germany
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  • This work is dedicated to Professor Rudolf Rott on the occasion of his 60th birthday.

Abstract

We studied cell-mediated cytotoxicity to hepatitis A virus-infected cells in seven patients with acute type A hepatitis and two controls. Skin fibroblast cultures obtained from the skin biopsies of seven patients after acute hepatitis A virus infection and from two persons without history of current or past hepatitis A virus infection were inoculated with hepatitis A virus. Infection of fibroblast cultures always resulted in an inapparent, persistent infection with production and release of infectious hepatitis A virus. Peripheral blood lymphocytes were collected from the same patients at different times after onset of icterus and were stored in liquid nitrogen. Cytolytic activity of peripheral blood lymphocytes was determined by a microcytotoxicity assay using autologous 51Cr-labeled hepatitis A virus-infected and uninfected target cells. Cytotoxic peripheral blood lymphocytes capable of lysing autologous hepatitis A virusinfected skin fibroblasts were detected in all patients with hepatitis A but were not demonstrable in the controls without antibodies against hepatitis A virus. The clinical course of the hepatitis A virus infection was normal in five patients; and in these patients, cytolytic activity of peripheral blood lymphocytes against hepatitis A virus-infected autologous targets peaked 2 to 3 weeks after onset of icterus. A clinically protracted form of the disease with persistent elevation of aminotransferase for at least 5 months after onset was present in two patients. In these cases, the highest cytolytic activity was demonstrated in peripheral blood lymphocytes collected 8 to 12 weeks after onset of icterus. Natural killer cell activity, as measured by specific lysis of K562 cells, did not show peak activity during the acute or convalescent phases of the disease. Our experimental findings suggest that cytolytic T cells play an important role in the pathogenesis of hepatitis A virus infection.

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