首页|Study of human B7 homolog 1 expression in patients with hepatitis B virus infection
Study of human B7 homolog 1 expression in patients with hepatitis B virus infection
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AIM:To further investigate the role of human B7 homolog 1 (B7-H1) in the mechanism of persistent hepatitis B virus (HBV) infection.METHODS:Peripheral and intra-hepatic B7-H1 expression were compared by flow cytometry and immunochemical staining between two 2 distinct groups,one being chronic HBV tolerance patients (CHB-T) and the other being acute hepatitis B patients (AHB).B7-H1 mRNA expression level was also compared by real time polymerase chain reaction between CHB-T and AHB patients.The location of intra-hepatic B7-H1 and CD40 expression were analyzed by immunofluorescence.The levels of B7-H1 and CD40 expression on cultured myeloid dendritic ceils (mDCs) with or without hepatitis B surface antigen (HBsAg) treatment were analyzed dynamically by flow cytometry.Intracellular interferon-γ (IFN-γ) staining and the stimulatory capacity of mDC of cultured mDC with or without HBsAg treatment were also compared by flow cytometry.RESULTS:Peripheral B7-H1 expression on mDCs was increased significantly in AHB compared to CHB-T patients (P ＜ 0.05).In the liver tissues from CHB-T patients,B7-H1 positive cells were almost absent despite a persistently elevated serum HBsAg load.In contrast,there were indeed increased B7-H1-positive cells in situ in the liver tissue from AHB.In vitro analysis showed the parallel upregulation of B7-H1 and CD40 on CD11c+ mDCs after the onset of stimulation.Addition of recombinant hepatitis B surface antigen (rHBsAg)significantly decreased CD40 expression (P ＜ 0.05 at 16 h,20 h and 24 h time points).B7-H1 expression was also inhibited by rHBsAg,and the inhibition rate of CD40 was greater than that of B7-H1.This preferential inhibition of CD40 expression on mDCs by rHBsAg resulted in the dysfunction of mDCs and T cells in the mixed leucocyte reaction (MLR) system.With rHBsAg pretreatment,in a carboxyfluorescein diacetate succinimidyl ester (CFSE) labeled MLR system at a ratio of 1∶5responder cell-stimulator cell (R/S),the CFSEdim percentage of T cells decreased from 85.1％ to 25.4％ and decreased from 30.3％ to 12.0％ at 1:10 R/S.IFN-γ,production by CD8+ T cells,in the MLR system,was reduced significantly by HBsAg pretreatment.At ratios of 1:5 R/S,the percentage of IFN-γ,and CD8 dual positive T cells decreased from 55.2％ ± 5.3％ to 15.1％ ±3.1％ (P ＜ 0.001),and decreased from 35.0％ ± 5.1％to 7.3％ ± 2.7％ at ratios of 1:10 R/S (P ＜ 0.001).CONCLUSION:B7-H1 is not a signature of immune dysfunction,but an inflammation marker.HBsAg regulate immune response by tipping the balance between B7-H1 and CD40.
Hepatitis B virusHepatitis BHuman B7 homolog 1Immune toleranceCo-stimulatory molecule
Wen-Jin Zhang、Hai-Yang Xie、Xin Duan、Yun-Le Wan、Chuan-Hui Peng、Shao-Hua Shi、Rong Su
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Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University,Hangzhou 310003, Zhejiang Province, China
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, Zhejiang Province, China
Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120,Guangdong Province, China
国家自然科学基金重点项目Zhejiang Provincial Natural Science FoundationZhejiang Provincial Natural Science Foundation
NETL
NSTL
万方数据
维普
