Therapeutic potential of dendritic cell-based immunization against HBV in transgenic mice.
Hepatitis B virus (HBV) transgenic mice that express HBV envelope proteins represent a model of chronic HBV infection suitable for the development of therapeutic immunization strategies. To address immunologically therapeutic effects induced by peptide-pulsed DCs, HBV transgenic mice were immunized with peptide-pulsed DCs, and the mice were killed after three times of immunization and the splenocytes were stimulated in vitro and detected by IFN-gamma ELISPOT and cytotoxic T lymphocyte (CTL) activity. The data demonstrated that HBV-specific CD8+ T cell response could be induced and CD8+ T cells had specific CTL activity. Furthermore, ELISA and fluorescent quantitative PCR were performed to detect the level of serum HBsAg and HBV DNA and the results demonstrated that HBV-specific peptide-pulsed DCs could significantly reduce the concentration of serum HBsAg and HBV DNA. The serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were measured and no significant differences were observed between the different groups, which indicated that no hepatocellular injury occurred. Taken together, the data strongly demonstrated that CD8+ T cell responses and antiviral immunity were elicited in HBV transgenic mice, suggesting that peptide-pulsed DCs could elicit an effective antiviral immunity.
Jiang
Wen-Zheng
WZ
School of Life Science, East China Normal University, Shanghai 200062, People's Republic of China. wzjiang@bio.ecnu.edu.cn
Fan
Yan
Y
Liu
Xia
X
Zhang
Ya-Li
YL
Wen
Jie-Jun
JJ
Hao
Wen-Li
WL
Qian
Min
M
D000818:Animals; D003602:Cytotoxicity, Immunologic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000276:immunology* / Q000628:therapy / Q000821:virology; D007114:Immunization; D007167:Immunotherapy; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D006514:Hepatitis B Surface Antigens; D007371:Interferon-gamma