title: Immunosuppressive functions of hepatic myeloid-derived suppressor cells of normal mice and in a murine model of chronic hepatitis B virus.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Toon City, Ehime, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: S M F
authors.initials: SM
authors.lastname: Akbar
authors.forename: M
authors.initials: M
authors.lastname: Abe
authors.forename: Y
authors.initials: Y
authors.lastname: Hiasa
authors.forename: M
authors.initials: M
authors.lastname: Onji
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology* / Q000821:virology; D004195:Disease Models, Animal; D005434:Flow Cytometry; D016679:Genome, Viral; D006514:Hepatitis B Surface Antigens / Q000032:analysis / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D007108:Immune Tolerance; D007118:Immunoassay; D007165:Immunosuppression Therapy; D007371:Interferon-gamma / Q000032:analysis / Q000096:biosynthesis; D008099:Liver / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology*; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000821:virology
chemical_list: D006514:Hepatitis B Surface Antigens; D007371:Interferon-gamma