Regulatory T cells contribute to the impaired immune response in patients with chronic hepatitis B virus infection

Authors

  • Jeroen N. Stoop,

    1. Department of Gastroenterology and Hepatology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
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    • J.N.S. and R.G.vdM. contributed equally to the study.

  • Renate G. van der Molen,

    Corresponding author
    1. Department of Gastroenterology and Hepatology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
    • Department of Gastroenterology and Hepatology, Erasmus MC–University Medical Center Rotterdam, Dr. Molewaterplein 40, Room L-448, 3015 GD Rotterdam, The Netherlands
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    • J.N.S. and R.G.vdM. contributed equally to the study.

    • fax: (31) 10-4632793

  • Carla C. Baan,

    1. Department of Internal Medicine, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
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  • Luc J. W. van der Laan,

    1. Department of Surgery, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
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  • Ernst J. Kuipers,

    1. Department of Gastroenterology and Hepatology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
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  • Johannes G. Kusters,

    1. Department of Gastroenterology and Hepatology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
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  • Harry L. A. Janssen

    1. Department of Gastroenterology and Hepatology, Erasmus MC–University Medical Center Rotterdam, Rotterdam, The Netherlands
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    • H.L.A.J. is a clinical fellow of the Netherlands Organization of Scientific Research (The Hague, The Netherlands).


  • See Editorial on Page 700.

  • Potential conflict of interest: Nothing to report.

Abstract

Chronic hepatitis B virus (HBV) infection is characterized by a weak immune response to HBV. Regulatory T cells (Treg) can suppress the function of effector T cells and may thus be key players in this impaired immune response. Changes in the functionality or number of Treg could explain the decreased antiviral response in chronic HBV patients. To investigate the role of Treg in chronic HBV infection, we compared the proportional frequency and functionality of Treg in peripheral blood of 50 chronic HBV patients, 23 healthy controls, and 9 individuals with a resolved HBV infection. A higher percentage of Treg, defined as CD4, CD25, CD45RO, and cytotoxic T-lymphocyte–associated antigen 4–positive cells, was detected within the population of CD4+ cells in peripheral blood of chronic HBV patients compared with healthy controls and individuals with a resolved HBV infection. Accordingly, chronic HBV patients displayed a higher FoxP3 messenger RNA level than healthy controls. Depletion of CD25+ cells from peripheral blood mononuclear cells (PBMC) of chronic HBV patients resulted in an enhanced proliferation after stimulation with HBV core antigen. Reconstitution of these depleted PBMC with CD4+CD25+ Treg resulted in a dose-dependent reduction of both HBV-specific proliferation and interferon γ production. In conclusion, chronic HBV patients harbor an increased percentage of Treg in peripheral blood compared with controls. Treg have an immunosuppressive effect on HBV-specific T helper cells. The presence of HBV-specific Treg could contribute to an inadequate immune response against the virus, leading to chronic infection. (HEPATOLOGY 2005;41:771–778.)

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