title: [Elevated expression of lymphocyte activation gene-3 on peripheral blood CD8(+) T lymphocytes in patients with chronic hepatitis B virus infection].
abstract: OBJECTIVE
  To evaluate the relationships between lymphocyte activation gene-3 (LAG-3) expression levels on peripheral blood T lymphocytes and other hepatitis related laboratory indexes (ALT, HBeAg and HBV DNA) in the different phases of the natural course of chronic hepatitis B virus (HBV) infection.
  
  
  METHODS
  The study enrolled 24 chronic HBV-infected patients in the immune-tolerant (IT) phase, 32 in the immune clearance (IC) phase, 31 in the inactive or low replication (LR) phase and 30 healthy control individuals (HC). The LAG-3 expression levels on peripheral blood T lymphocytes were measured by flow cytometry. Biochemical analyses, immunoassay and polymerase chain reaction (PCR) were used to detect the liver function, serological markers of HBV and HBV DNA viral copies, respectively. Mann-Whitney U test was used to compare the expression levels of LAG-3 in groups. Spearman correlation analysis was performed to analyze the relationships between the serum levels of ALT, HBeAg, HBV DNA and the positive expression rate of LAG-3.
  
  
  RESULTS
  A statistically higher ratio of LAG-3+CD8+ T cells was confirmed in chronic HBV-infected patients than in healthy controls. Patients in the IT phase of chronic HBV infection had even higher ratio of LAG-3+CD8+ T cells than those in the IC phase or the LR phase. The ratios of peripheral blood LAG-3+CD8+ T cells and LAG-3+CD4+ T cells in the IC phase of chronic HBV-infection were negatively correlated with the serum ALT level. The ratios of peripheral blood LAG-3+CD8+ T cells and LAG-3+CD4+ T cells in the IT phase of chronic HBV-infection were positively correlated with the serum HBeAg level. There was no correlation between the ratio of peripheral blood LAG-3+CD4+ T cells or LAG-3+CD8+ T cells and HBV DNA viral copies in chronic HBV-infected patients.
  
  
  CONCLUSIONS
  LAG-3, an immunoinhibitory receptor, is highly expressed in peripheral blood CD8+ T cells in chronic HBV-infected patients, especially in the patients experiencing IT phase. The high expression level of LAG-3 on CD8+T cells might be one of the vital immune factors leading to the dysfunction of CD8+T cells and the continuous replication of HBV in the patients with chronic HBV infection.
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, Second Military Medical University, Shanghai 200433; Department of Laboratory Medicine, Shanghai Seventh People's Hospital, Shanghai 200137, China.
authors.forename: Chenyun
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of Laboratory Medicine, Shanghai Seventh People's Hospital, Shanghai 200137, China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Laboratory Medicine, Shanghai Seventh People's Hospital, Shanghai 200137, China.
authors.forename: Kexiang
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Laboratory Medicine, Shanghai Seventh People's Hospital, Shanghai 200137, China.
authors.forename: Lihan
authors.initials: L
authors.lastname: Bie
authors.affiliation: Department of Laboratory Medicine, First Affiliated Hospital, Second Military Medical University, Shanghai 200433, China. *Corresponding author, E-mail: shenq611@163.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Shen
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D005260:Female; D019694:Hepatitis B, Chronic / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D015854:Up-Regulation; D055815:Young Adult; D000093322:Lymphocyte Activation Gene 3 Protein
chemical_list: D015703:Antigens, CD; D000093322:Lymphocyte Activation Gene 3 Protein; C000720326:Lag3 protein, human