HBV genes induce cytotoxic T-lymphocyte response upon adeno-associated virus (AAV) vector delivery into dendritic cells
Autor: | Dazhi Zhang, Changxuan You, P. L. Hermonat, Min Cong, W. Ping, J. L. Mehta, Hong You, Yong Liu |
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Rok vydání: | 2006 |
Předmět: |
Hepatitis B virus
Genes Viral viruses Genetic Vectors Biology medicine.disease_cause Major histocompatibility complex Cell Line Antigen Interferon Antigens CD Transduction Genetic Virology medicine Cytotoxic T cell Humans Adeno-associated virus Cells Cultured Hepatology Liver cell Dendritic Cells Dependovirus Cytotoxicity Tests Immunologic Flow Cytometry digestive system diseases CTL Infectious Diseases Immunology biology.protein medicine.drug T-Lymphocytes Cytotoxic |
Zdroj: | Journal of viral hepatitis. 13(9) |
ISSN: | 1352-0504 |
Popis: | Hepatitis B virus (HBV) has been an increasing problem throughout the world and remains difficult to treat. But immunotherapeutic approaches offer new, effective treatments. Three recombinant adeno-associated virus (AAV) type 2 vectors, carrying one of the HBV S, C or X gene, were used to load (transduce) professional antigen-presenting dendritic cells (DC) for the purpose of stimulating cytotoxic T lymphocytes (CTL) in vitro. It was found that all three recombinant AAV/HBV antigen virus loaded DC at approximately 90% transduction efficiency. Most importantly, all three AAV-loaded DC stimulated rapid, antigen-specific and major histocompatibility complex (MHC)-restricted CTL. In vitro, these CTL killed (30-50%) synthetic antigen-positive autologous targets as well as HepG2 liver cell targets. In comparing the three antigens, it was found that AAV/HBV-C-derived CTL consistently had the highest killing efficiency. CTL derived from AAV/HBV-C-loaded DC also showed significantly higher killing of targets than that from bacterially generated C-protein-loaded DC. Further studies showed that AAV/HBV-C-derived CTL had higher interferon (IFN)-gamma. These data suggest that AAV/HBV antigen gene-loading of DC may be useful for immunotherapeutic protocols against HBV infection and that the HBV C antigen may be the most useful for this purpose. |
Databáze: | OpenAIRE |
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