Hepatitis B virus gives rise to chronic infection in 350 million people world wide, and infection can result in the development of liver cirrhosis, liver failure or hepatocellular carcinoma. Current therapies merely treat the infection and prevent progression, because there is no cure. There have been promising studies in the clearance of HBV DNA in murine models with the use of iNKT stimulating lipid αGalCer. However, iNKT stimulation of αGalCer has not been an effective measure in anti-viral or anti-cancer clinical trials. It is speculated that these differences between human and mouse reactivity to αGalCer is based on the differences of CD1d/NKT lipid presentation systems between the two species. Previously, our lab has generated an hCD1d KI model to support a human like NKT cell environment. In order to investigate the role of invariant NKT cells in HBV and to allow us to test potential therapeutic lipids for HBV in a more human like environment, we generated a novel HBVtg hCD1d-KI model. Thus in this study we seek to characterize the population of iNKT cells in this new HBVtg hCD1d-KI model. As reported in human chronic HBV patients, we found that the iNKT cells are significantly lower in this new HBV-transgenic model. Among the decreased levels of iNKT cells, there was a significant decrease in the population of CD4+ iNKT cells accompanied by a significant increase of CD4- iNKT cells. Similarly, there was an overall significant decrease of total NKT Cells. There was an overall increase in CD8+ conventional T Cells, and a significant increase of total conventional T cells. Our study also found that conventional T cells had and significant upregulation of PD-1, which was restricted to the CD8+ population. In our study, the levels of PD-1 among the iNKT cell populations were not affected; suggesting the decrease of iNKT cells was not related to PD-1 expression. Altogether, our results support that our new HBVtg can a useful new model for study of HBV pathogenesis as well as exploration and validation of novel anti-HBV therapeutic approaches.
|Commitee:||Ou, James, Schonthal, Axel|
|School:||University of Southern California|
|Department:||Molecular Microbiology and Immunology|
|School Location:||United States -- California|
|Source:||MAI 52/03M(E), Masters Abstracts International|
|Subjects:||Cellular biology, Virology, Immunology|
|Keywords:||HBV, HBVtg, Humanized, NKT cells, hCD1d-KI, iNKT|
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