title: High frequency of CD4+ CXCR5+ TFH cells in patients with immune-active chronic hepatitis B.
abstract: BACKGROUND
  T follicular helper (TFH) cells are a special subpopulation of T helper cells and can regulate humoral immune responses. This study examined whether the frequency of CD4(+)CXCR5(+) TFH cells could be associated with active immunity in chronic hepatitis B (CHB) patients.
  
  
  RESULTS
  The frequencies of peripheral blood CD4(+)CXCR5(+) TFH cells, inducible T cell costimulator (ICOS), and/or programmed death 1 (PD-1) positive CD4(+)CXCR5(+) TFH cells in immune-active (IA), immune-tolerant (IT) CHB, and healthy controls (HC) were characterized by flow cytometry analysis. The effect of adevofir dipivoxil treatment on the frequency of CD4(+)CXCR5(+) TFH cells, the concentrations of serum IL-2, IFN-γ, TNF-α, IL-4, IL-6, IL-10, IL-21, ALT, AST, HBsAg, HBsAb, HBeAg, HBeAb and HBV loads in IA patients were determined. The potential association of the frequency of CD4(+)CXCR5(+) TFH cells with clinical measures was analyzed. In addition, the frequency of splenic and liver CD4(+)CXCR5(+) TFH cells in HBV-transgenic mice was examined. We found that the frequency of CD4(+)CXCR5(+) TFH cells in IA patients was significantly higher than that of IT patients and HC, and the percentages of CD4(+)CXCR5(+) TFH in IA patients were positively correlated with AST. Furthermore, the percentages of ICOS(+), PD-1(+), and ICOS(+)PD-1(+) in CD4(+)CXCR5(+) TFH cells in CHB patients were significantly higher than that of HC. Treatment with adefovir dipivoxil reduced the frequency of CD4(+)CXCR5(+) TFH, PD-1(+)CD4(+)CXCR5(+) TFH cells and the concentrations of HBsAg and HBeAg, but increased the concentrations of HBsAb, HBeAb, IL-2 and IFN-γ in IA patients. Moreover, the frequency of splenic and liver CD4(+)CXCR5(+) TFH cells in HBV-transgenic mice was higher than that of wild-type controls.
  
  
  CONCLUSIONS
  These data indicate that CD4(+)CXCR5(+) TFH cells may participate in the HBV-related immune responses and that high frequency of CD4(+)CXCR5(+) TFH cells may be a biomarker for the evaluation of active immune stage of CHB patients.
authors.affiliation: Department of Central Laboratory, the Second Part of First Hospital, Jilin University, Changchun, China.
authors.forename: Junyan
authors.initials: J
authors.lastname: Feng
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Cong
authors.initials: C
authors.lastname: Hua
authors.forename: Ling
authors.initials: L
authors.lastname: Qin
authors.forename: Pingwei
authors.initials: P
authors.lastname: Zhao
authors.forename: Juan
authors.initials: J
authors.lastname: Wang
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Wanyu
authors.initials: W
authors.lastname: Li
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Shi
authors.forename: Yanfang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects / Q000276:immunology; D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D015704:CD4 Antigens / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006515:Hepatitis B virus / Q000187:drug effects / Q000235:genetics / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use; D054380:Receptors, CXCR5 / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D015704:CD4 Antigens; C095085:CXCR5 protein, human; D016207:Cytokines; D004279:DNA, Viral; D063065:Organophosphonates; D054380:Receptors, CXCR5; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000225:Adenine; C106812:adefovir dipivoxil