Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus

Authors

  • S. Chen,

    1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon City, Ehime
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  • S. M. F. Akbar,

    1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon City, Ehime
    2. Department of Medical Sciences, Toshiba General Hospital, Tokyo, Japan
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  • M. Abe,

    1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon City, Ehime
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  • Y. Hiasa,

    1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon City, Ehime
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  • M. Onji

    Corresponding author
    1. Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon City, Ehime
      Morikazu Onji, Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime 791-0295, Japan. E-mail: sheikh.akbar@po.toshiba.co.jp
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Morikazu Onji, Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Shitsukawa 454, Toon City, Ehime 791-0295, Japan. E-mail: sheikh.akbar@po.toshiba.co.jp

Summary

The immunosuppressive state of tumour-bearing hosts is attributable, at least in part, to myeloid-derived suppressor cells (MDSC). However, the role of MDSC in physiological conditions and diseases other than cancer has not been addressed. As the liver is a tolerogenic organ, the present study attempted to localize and assess functions of hepatic MDSC in a normal liver and in a murine model of chronic hepatitis B virus (HBV) infection. MDSC was identified in the liver of normal mice and HBV transgenic mice (TM) as CD11b+ Gr1+ cells by dual-colour flow cytometry. Highly purified populations of MDSC and their subtypes were isolated by fluorescence-activated cell sorting. The functions of MDSC and their subtypes were evaluated in allogenic mixed lymphocyte reaction (MLR) and hepatitis B surface antigen (HBsAg)-specific T cell proliferation assays. Normal mice-derived liver MDSC, but not other myeloid cells (CD11b+ Gr1-), suppressed T cell proliferation in allogenic MLR in a dose-dependent manner. Alteration of T cell antigens and impaired interferon-γ production seems to be related to MDSC-induced immunosuppression. In HBV TM, the frequencies of liver MDSC were about twice those of normal mice liver (13·6 ± 3·2% versus 6·05 ± 1·21%, n = 5, P < 0·05). Liver-derived MDSC from HBV TM also suppressed proliferative capacities of allogenic T cells and HBsAg-specific lymphocytes. Liver MDSC may have a critical role in maintaining homeostasis during physiological conditions. As liver MDSC had immunosuppressive functions in HBV TM, they may be a target of immune therapy in chronic HBV infection.

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