The Immune Modulatory Function of the Hepatitis B Virus e Antigen (HBeAg)

• Main Authors: Jeng-chiao Kuo, 郭正佼
• Other Authors: Cheng-po Hu
• Format: Others
• Language: en_US
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/66637623711528029816

碩士 === 國立陽明大學 === 微生物暨免疫學研究所 === 90 === Hepatitis B virus causes acute and chronic infections of the liver. The chronic HBV carriers have a very high risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). HBeAg, a secretory product of HBV, has been suggested to play a role in helping HBV establish persistent infection. Previously, we found that HBeAg could bind to mouse peritoneal exudate cells (PEC) and Kupffer cells, and induced the expression of various cytokine genes. In order to access the role that HBeAg plays in HBV pathogenesis and its possible mechanism, in this study, we compared the effects of HBeAg on Kupffer cells, resident peritoneal cells (RPC) and thioglycollate- induced peritoneal exudate macrophages (PEM) to address the immune modulatory functions of HBeAg. Using flow cytometry and enzyme-linked immunosorbent assay (ELISA), we demonstrated that HBeAg did not alter the expression of MHC class I, class II, B7.1 (CD80) and B7.2 (CD86) on Kupffer cells, but induced the production of various mediators including IL-1b, IL-6, IL-10, IL-12, IFN-g, MCP-1 and PGE2. However, the HBeAg-induced mediator production was dependent on the origin and the activation state of macrophages. For example, HBeAg stimulated resting Kupffer cells and RPC to secrete a large amount of IL-10, but stimulated activated PEM to secrete a large amount of IL-12 instead of IL-10. In order to compare the effects of HBeAg to those of bacterial lipopolysaccharide (LPS), C3H/HeJ mice that have mutations in their Toll-like receptor 4 gene (Tlr4) and are hyporesponsive to LPS were used. We demonstrated that HBeAg interacted with TLR4 or/and TLR4-associated molecules on the surface of Kupffer cells, splenic macrophages and B cells. Thus, HBeAg might execute its functions by influencing the host’s innate immune responses and help virus develop persistent infection.