title: Inhibition of HBV Replication in HepG2.2.15 Cells by Human Peripheral Blood Mononuclear Cell-Derived Dendritic Cells.
abstract: Anti-HBV therapy is essential for patients awaiting liver transplantation. This study aimed to explore the effects of dendritic cells (DCs) derived from the peripheral blood of hepatitis B patients on the replication of HBV in vivo and to evaluate the biosafety of DCs in clinical therapy. Peripheral blood mononuclear cells (PBMCs) were isolated from HBV-infected patients and maturation-promoting factors and both HBsAg and HBcAg were used to induce DC maturation. Mature DCs and lymphocytes were co-cultured with human hepatocyte cell HL-7702 or HBV-producing human hepatocellular carcinoma cell HepG2.2.15. We found that mature lymphocytes exposed to DCs in vitro did not influence morphology or activities of HL-7702 and HepG2.2.15 cells. Liver function indexes and endotoxin levels in the cell supernatants did not change in these co-cultures. Additionally, supernatant and intracellular HBV DNA levels were reduced when HepG2.2.15 cells were co-cultured with mature lymphocytes that had been cultured with DCs, and HBV covalently closed circular DNA (cccDNA) levels in HepG2.2.15 cells also decreased. Importantly, DC-mediated immunotherapy had no mutagenic effect on HBV genomic DNA by gene sequencing of the P, S, X, and C regions of HBV genomic DNA. We conclude that PBMC-derived DCs from HBV-infected patients act on autologous lymphocytes to suppress HBV replication and these DC clusters showed favorable biosafety.
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Song
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zheng
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China hlsong26@sina.com.
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Shen
mesh_terms: D064987:Cell- and Tissue-Based Therapy / Q000379:methods; D018920:Coculture Techniques; D017077:Culture Media, Conditioned / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis / Q000235:genetics; D003713:Dendritic Cells / Q000502:physiology* / Q000821:virology; D004731:Endotoxins / Q000032:analysis; D056945:Hep G2 Cells / Q000821:virology; D006509:Hepatitis B / Q000097:blood / Q000628:therapy; D006515:Hepatitis B virus / Q000472:pathogenicity / Q000502:physiology*; D022781:Hepatocytes / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008213:Lymphocyte Activation; D014779:Virus Replication / Q000502:physiology*
chemical_list: D017077:Culture Media, Conditioned; D004279:DNA, Viral; D004731:Endotoxins
keywords: HBV genome sequence; HepG2.2.15; biosafety; dendritic cells; hepatitis B virus