Frequencies and Characterization of HBV-specific Cytotoxic T Lymphocytes in Self-limited and Chronic Hepatitis B Viral Infection in China  

作　　者：杨新星 郝友华 刘贽 陈玲 丁红晖 赵西平 陆蒙吉 杨东亮 

机构地区：[1]Division of Clinical Immunology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology [2]Deparment of Infectious Diseases,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology [3]Department of Microbiology,Tongji Medical College,Huazhong University of Science and Technology [4]Institute of Virology,Medical School of Duisburg-Essen University

出　　处：《Journal of Huazhong University of Science and Technology(Medical Sciences)》2009年第5期567-574,共8页华中科技大学学报（医学英德文版）

基　　金：supported by grants from the National Key Basic Research Program of China (No.20014CB510008,No.2005CB522901);the National Natural Sciences Foundation of China (No.30400412)

摘　　要：Hepatitis B virus （HBV）-specific cytotoxic T lymphocytes （CTLs） are believed to play a major role in viral clearance and disease pathogenesis during HBV infection. To clarify the differences in host immune responses between self-limited and chronic HBV infections, we constructed three HLA-A＊0201/HBV tetramers with immunodominant epitopes of core18-27, polymerase 575-583 and envelope 335-343, and analyzed the HBV-specific CTLs in peripheral blood mononuclear cells （PBMCs） from patients infected with HBV. The frequencies and expansion ability of HBV-specific CD8＋T cells in most self-limited HBV infected individuals were higher than those in chronic HBV-infected patients. HBV-specific CD8＋T cells could be induced by in vitro peptide stimulation from chronic patients with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. In chronic infection, no significant correlation was found either between the frequencies of HBV-specific CD8^＋ T cells and the viral load, or between the frequencies and the levels of alanine transaminase. Our results suggested that the frequencies of HBV-specific CTLs are not the main determinant of immune-mediated protection in chronic HBV infection and immunotherapeutic approaches should be aimed at not only boosting a HBV-specific CD8^＋T response but also improving its function.Hepatitis B virus （HBV）-specific cytotoxic T lymphocytes （CTLs） are believed to play a major role in viral clearance and disease pathogenesis during HBV infection. To clarify the differences in host immune responses between self-limited and chronic HBV infections, we constructed three HLA-A＊0201/HBV tetramers with immunodominant epitopes of core18-27, polymerase 575-583 and envelope 335-343, and analyzed the HBV-specific CTLs in peripheral blood mononuclear cells （PBMCs） from patients infected with HBV. The frequencies and expansion ability of HBV-specific CD8＋T cells in most self-limited HBV infected individuals were higher than those in chronic HBV-infected patients. HBV-specific CD8＋T cells could be induced by in vitro peptide stimulation from chronic patients with a low level of serum HBV-DNA but not from those with a high level of serum HBV-DNA. In chronic infection, no significant correlation was found either between the frequencies of HBV-specific CD8^＋ T cells and the viral load, or between the frequencies and the levels of alanine transaminase. Our results suggested that the frequencies of HBV-specific CTLs are not the main determinant of immune-mediated protection in chronic HBV infection and immunotherapeutic approaches should be aimed at not only boosting a HBV-specific CD8^＋T response but also improving its function.

关 键 词：hepatitis B virus cytotoxic T lymphocyte HLA-A＊0201 

分 类 号：R512.62[医药卫生—内科学]