Li-Min Chen 12
Xue-Gong Fan 1 Email author
Jing Ma 3
Bo He 3
Yong-Fang Jiang 3 Email author
1.Infectious Diseases InstituteThe Xiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
2.Infectious Diseases InstituteThe Third Xiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
3.Liver Diseases Research CenterThe Second Xiangya Hospital, Central South UniversityChangshaPeople’s Republic of China
Original Article
First Online:
18 May 2016
DOI: 10.1007/s12072-016-9734-5
Cite this article as:
Chen, LM., Fan, XG., Ma, J. et al. Hepatol Int (2017) 11: 79. doi:10.1007/s12072-016-9734-5
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Abstract
Purpose
The aim of this study is to investigate the T-lymphocyte subpopulation and expression of programmed cell death-1 (PD-1), toll-like receptor (TLR)3, TLR4, and interferon (INF)-γ to illustrate the relationship between hepatitis B e antigen (HBeAg) and persistent hepatitis B virus (HBV) infection.
Methods
Blood was taken from normal subjects into anticoagulation tubes to separate peripheral blood mononuclear cells (PBMCs). The PBMCs were divided into four groups and cultured with various concentrations of HBeAg for 72 h. Changes in the T-cell subset were analyzed through cell counting by flow cytometry, and expression of TLR3, TLR4, and PD-1 was assessed by flow cytometry and Western blot. The concentration of IFN-γ was analyzed using enzyme-linked immunospot (ELISPOT) experiments.
Results
PBMCs were stimulated with various concentrations of HBeAg for 72 h and assayed by flow cytometry to determine CD4+ and CD8+ cell counts. The relative frequencies of CD4+ and CD8+ subpopulations and the CD4+/CD8+ ratio decreased compared with the control group, and T-cell impairment was significantly associated with higher HBeAg load. TLR3, TLR4, and PD-1 protein expression was assessed using flow cytometry and Western blotting. Expression of TLR3, TLR4, and PD-1 increased with increasing concentration of HBeAg. ELISPOT experiments were used to determine the concentration of IFN-γ. IFN-γ production in treatment groups was lower than in the control group. Comparing IFN-γ production in treatment groups, IFN-γ production in PBMCs stimulated with high dose of HBeAg was lower than for those stimulated with low-dose HBeAg.
Conclusions
HBeAg can inhibit proliferation of lymphocytes, increase TLR3, TLR4, and PD-1 expression, and decrease IFN-γ production. This may be one of the molecular mechanisms of HBV immune tolerance.
Keywords
Hepatitis B e antigen Toll-like receptor 3 Toll-like receptor 4 Programmed cell death-1 Interferon-γ
X.-G. Fan and Y.-F. Jiang are equal contributors. 作者: StephenW 时间: 2017-1-23 18:15
肝病学国际
2017年1月,第11卷,第1期,第79-86页
HBeAg在持续性HBV感染中的分子机制
李敏摘要:摘要:摘要:
李敏民12
Xue-Gong Fan 1电子邮件作者
静马3
Bo He 3
Yong-Fang Jiang 3电子邮件作者