title: Expansion of circulating TFH cells and their associated molecules: involvement in the immune landscape in patients with chronic HBV infection.
abstract: BACKGROUND
  Blood CXCR5+CD4+ T cells are defined as circulating T follicular helper (TFH) cells, which is required for effective humoral immunity. This study aimed to investigate the role of circulating TFH cells in patients with chronic hepatitis B virus (CHB) infection.
  
  
  METHODS
  The frequency and phenotype of circulating TFH cells were monitored by flow cytometry in CHB patients and in healthy controls (HC). The expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA was analyzed using real-time PCR. Serum HBsAg, HBeAg, HBeAb, HBV DNA loads, ALT and AST were determined. The potential association of the frequency of TFH cells and their surface markers with clinical parameters was assessed.
  
  
  RESULTS
  The frequency of CXCR5+CD4+ T cells was increased in CHB patients and positively correlated with ALT and AST but not with HBV DNA loads. Moreover, an expansion of ICOS-, PD-1-, CD40L-, and IL-21R-expressing TFH cells occurred in CHB patients, but failed to correlate with ALT, AST and HBV DNA loads. Interestingly, the frequency of CXCR5+CD4+ T cells and ICOS+CXCR5+CD4+ T cells was significantly higher in HBeAg positive CHB patients than in HC. Additionally, the percentages of CXCR5+CD4+ T cells were positively correlated with AST, and ICOS-expressing CXCR5+CD4+ T cells were negatively correlated with HBV DNA loads. No significant differences in the frequency of CXCR5+CD4+ T cells were observed between inactive carrier (IC) patients and healthy controls. However, ICOS-, PD-1-, CD40L-expressing TFH cells were increased in IC patients and positively correlated with AST. Furthermore, the expression of BCL-6, IL-21, IL-4, CXCR5, and IL-6R mRNA in TFH cells was higher in CHB patients than in HC.
  
  
  CONCLUSIONS
  These data demonstrate that circulating TFH cells may participate in HBV-related immune responses. In addition to the frequency of TFH cells, the phenotype of these cells plays an important role in CHB patients.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Hu
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Song
authors.forename: Yu
authors.initials: Y
authors.lastname: Lei
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Hu
authors.forename: Hong
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, 74# Linjiang Road, Yuzhong District, Chongqing 400010, China. hp_cq@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
mesh_terms: D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000737:chemistry / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006511:Hepatitis B Antigens / Q000097:blood; D019694:Hepatitis B, Chronic / Q000276:immunology*; D006801:Humans; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*; D055815:Young Adult
chemical_list: C084103:BCL6 protein, human; C095085:CXCR5 protein, human; D004279:DNA, Viral; D004268:DNA-Binding Proteins; D006511:Hepatitis B Antigens; D007378:Interleukins; D051560:Proto-Oncogene Proteins c-bcl-6; D054380:Receptors, CXCR5