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- W3148784858 abstract "a foreign antigenic polyepitope into liver and subsequently attract strong polyepitope-specific immune responses. Methods: A DNA fragment encoding HLA-A2 and HLA-DR binding epitopes was fused in frame to the core gene of HBV to create a pseudo-virus, which could self-maintain in hepatocytes with the capsid complemented in trans by wild type HBV in infected cells, as demonstrated by cotransfection assay in vitro. Results: Expression of the foreign polyepitope and HBsAg was detected in mouse liver after hydrodynamic injection of a DNA plasmid encoding 1.3 copy of rHBV. Immunization of HLA-A2/DR1 transgenic mice with a plasmid encoding the polyepitope primed specific interferon g (INFg)-secreting effector T cells in periphery. Subsequent injection of rHBV by hydrodynamic route induced a relocalization of these T cells to the liver as demonstrated by HLA-A2 tetramer staining and histological examination of liver sections. Most liver infiltrating CD8+ T cells were functional effectors, secreting INFg and undergoing degranulation upon peptide stimulation. Following priming and hydrodynamic injection of rHBV, HBsAg expression in mouse liver, as well as HBsAg in serum, was mostly inhibited without apparent liver injury, suggesting a non-cytolytic control by polyepitope-specific T cells. Experiments performed in HLA-A2/HBsAg transgenic mice also confirmed this hypothesis. Conclusions: Since rHBV can only replicate in hepatocytes bearing the wild type HBV, we expect that the robust immune response elicited in liver by the foreign polyepitope will dominate over the exhausted immune response during natural HBV persistent infection." @default.
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- W3148784858 date "2010-01-01" @default.
- W3148784858 modified "2023-10-15" @default.
- W3148784858 title "89 SEQUENTIAL ACTIVATION OF CXCR3 AND CCR6 MEDIATES RECRUITMENT AND POSITIONING OF INTERLEUKIN 17 PRODUCING T CELLS IN THE LIVER" @default.
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