The effects of T cell immunity on the production and maintenance of HBV core antibody

• Main Authors: Yi-Ting Kup, 郭奕廷
• Other Authors: Hung-Chih Yang
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/53538162888799598348

碩士 === 國立臺灣大學 === 微生物學研究所 === 102 === More than 240 million people have chronic Hepatitis B virus (HBV) infection, and about 600,000 people die due to acute or chronic HBV infection every year. The therapeutic course of chronic HBV infection is very long. Viral relapse is common when anti-virus treatment is stopped. There is no indicator providing the doctor with confidence to know when to stop the therapeutic course. Clearance of hepatitis infection relies on the host immunity, so the quality of host immunity, particularly T cell immunity, should be a good indicator for prognosis before treatment. However, measurement of T cell immunity, such as counting cytokine-secreting cells by enzyme-linked immunospot (ELISPOT) or HLA-restriction cells by the tetramer staining, is expensive and labor-intensive. Therefore, development of a convenient and inexpensive indicator that appropriately represents the strength of T cell immunity is in pressing need. In 2013 Yuan and his colleagues analyzed the anti-core antibody levels of chronic hepatitis B patients and healthy individuals. They found the anti-core antibody titer of chronic hepatitis B patients with elevated Alanine Aminotransferase (ALT) levels is significantly higher than that of those with normal ALT levels. This observation suggested that the level of anti-core antibody might be a good indicator of T cell immunity. By using the hydrodynamic injection mouse model, we found the levels of anti-core antibody peaked at day 7 after hydrodynamic injection and dropped sharply to about 10 IU/ml. Compared to the hydrodynamic mouse model, the levels of anti-core antibody increased slowly in mice receiving DNA vaccine. To mimic liver damage in chronic hepatitis B infection, we used Thioacetamide(TAA) in the hydrodynamic mouse model. The anti-core antibody increased dramatically after TAA treatment. The result revealed that liver damage would affect the anti-core antibody response. Depletion of CD4 T cells had no impact on the anti-core antibody production in the primary response and in the TAA-induced liver damage in a hydrodynamic mouse model. To clarify the relationship between T cell immunity and the level of anti-core antibody, we adoptively transferred HBV-specific T cells to mice receiving hydrodynamical injection of the HBV-expressing plasmid. The clearance rate of HBV surface antigens in mice receiving HBV-specific T cells was faster than the control group. The anti-core antibody titer of mice to which HBV-specific T cells were adoptively transferred was higher at day 7 post transferring day. This result suggested that HBV-specific T cells including CD4 and CD8 populations were important in maintaining the anti-core antibody titer. Finally, hydrodynamic injection of the pAAV/HBV plasmid carrying Y132A mutation did not induce the anti-core antibody response. The previous study showed that the capsid structure was critical for the T cell-independent response. However, in a hydrodynamic model there was no antibody response by pAAV/HBV carrying Y132A mutation.