title: Immunization with adenovirus LIGHT-engineered dendritic cells induces potent T cell responses and therapeutic immunity in HBV transgenic mice.
abstract: LIGHT, a TNF superfamily member (TNFSF14), is a type II transmembrane protein expressed on activated T cells and immature dendritic cells (DCs). However, the expression of LIGHT on mature DCs is down-regulated. Recent studies demonstrated that LIGHT provides potent costimulatory activity for T cells, enhancing proliferation and the production of Th1 cytokines independently of the B7-CD28 pathway. Here, we evaluated the effectiveness of peptide-pulsed DC-mediated antiviral immunity in HBV transgenic mice and the immunoadjuvant effect of LIGHT. The bone marrow-derived DCs were modified in vitro with an adenovirus (Ad) vector expressing mouse LIGHT (Ad-LIGHT), the expression of costimulatory molecules was up-regulated and the secretion of cytokines IL-12 and IFN-γ increased. LIGHT-modified DCs enhanced allostimulation for T cells in mixed lymphocyte reaction (MLR). HBV peptide-pulsed DCs elicited HBV specific CD8+ T cell response and reduced the level of HBsAg and HBV DNA in sera of HBV transgenic mice. Importantly, LIGHT-modified DCs could induce stronger antiviral immunity. These results support the concept that genetic modification of DCs with a recombinant LIGHT adenovirus vector may be a useful strategy for antiviral immunotherapy.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China. Electronic address: wzjiang@bio.ecnu.edu.cn.
authors.forename: Wenzheng
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Ran
authors.initials: R
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Kong
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Fengying
authors.initials: F
authors.lastname: Long
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, School of Life Sciences, East China Normal University, Shanghai 200241, China.
authors.forename: Yaru
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D006514:Hepatitis B Surface Antigens / Q000097:blood; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007167:Immunotherapy / Q000379:methods*; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000235:genetics / Q000276:immunology*
chemical_list: D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D018664:Interleukin-12; D007371:Interferon-gamma
keywords: Cytotoxic T lymphocyte; Dendritic cell; Hepatitis B virus; LIGHT; Transgenic mice