title: Study of human B7 homolog 1 expression in patients with hepatitis B virus infection.
abstract: OBJECTIVE
  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 cells (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 1:5 responder cell-stimulator cell (R/S), the CFSE(dim) 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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China.
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Hai-Yang
authors.initials: HY
authors.lastname: Xie
authors.forename: Xin
authors.initials: X
authors.lastname: Duan
authors.forename: Yun-Le
authors.initials: YL
authors.lastname: Wan
authors.forename: Chuan-Hui
authors.initials: CH
authors.lastname: Peng
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Shi
authors.forename: Rong
authors.initials: R
authors.lastname: Su
authors.forename: Zhang-Hui
authors.initials: ZH
authors.lastname: Zheng
authors.forename: Le-Lin
authors.initials: LL
authors.lastname: Pan
authors.forename: Lin
authors.initials: L
authors.lastname: Zhou
authors.forename: Shu-Sen
authors.initials: SS
authors.lastname: Zheng
mesh_terms: D060890:B7-H1 Antigen / Q000096:biosynthesis*; D019013:CD40 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured / Q000166:cytology; D003713:Dendritic Cells / Q000821:virology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D015967:Gene Expression Regulation, Viral; D006509:Hepatitis B / Q000378:metabolism* / Q000821:virology*; D006514:Hepatitis B Surface Antigens / Q000378:metabolism; D006515:Hepatitis B virus / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007371:Interferon-gamma / Q000378:metabolism; D007959:Lymphocyte Culture Test, Mixed; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology
chemical_list: D060890:B7-H1 Antigen; D019013:CD40 Antigens; D006514:Hepatitis B Surface Antigens; D012333:RNA, Messenger; D007371:Interferon-gamma