title: Circulating T follicular helper cells are associated with rapid virological response in chronic hepatitis C patients undergoing peginterferon therapy.
abstract: BACKGROUND
  Chronic hepatitis C virus (HCV) infection is associated with abnormal T cell and B cell immune responses. T follicular helper (TFH) cells are a subset of CD4(+) T-helper cells and can activate B cells. This study aimed to investigate the role of circulating CXCR5(+)CD4(+) TFH cells, CD19(+) B cells and the associated cytokines in patients with chronic HCV infection.
  
  
  METHODS
  The frequencies and phenotypes of circulating TFH cells and B cell subtypes were characterized using flow cytometry in chronic hepatitis C (CHC) patients and in healthy controls (HCs). The expression of IFN-γ, IL-12p70, IL-5, IL-13, IL-17F, IL-22, IL-23, TGF-β1, IL-10 and IL-21 associated with Th1, Th2, Th17, regulatory T cells (Treg) and TFH cells were analyzed using a Quantibody array. The patients' clinical parameters were detected, and the effect of pegylated interferon plus ribavirin treatment on these immune indicators in CHC patients was determined.
  
  
  RESULTS
  The frequency of CXCR5(+)CD4(+) T cells was significantly higher in CHC patients compared to HCs. There were no significant differences in CD19(+) B cells, CD19(+)CD27(+) B cells, or CD19(+)CD38(+) B cells between CHC patients and HCs. The expressions of cytokines associated with the CD4(+) Th lineage were higher in CHC patients than in HCs, except for IL-21. Patients with rapid virological response (RVR) showed an increased CXCR5(+)CD4(+) T cell count and decreased PD-1(+) CXCR5(+)CD4(+) T cell count compared to non-RVR patients after PEG-IFN/ribavirin treatment.
  
  
  CONCLUSIONS
  These data demonstrate that circulating TFH cells and CD4(+) Th lineage-associated cytokines may play a role in HCV-related immune responses.
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, Chongqing 400010, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Zhang
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, Chongqing 400010, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
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, Chongqing 400010, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Li
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, Chongqing 400010, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
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, Chongqing 400010, China.
authors.forename: Aoran
authors.initials: A
authors.lastname: Luo
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, Chongqing 400010, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
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, Chongqing 400010, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
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, Chongqing 400010, China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Peng
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, Chongqing 400010, China.
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, Chongqing 400010, China. Electronic address: hp_cq@163.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Hu
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005355:Fibrosis; D006526:Hepatitis C / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016898:Interferon-alpha / Q000627:therapeutic use; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D054380:Receptors, CXCR5 / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; C095085:CXCR5 protein, human; D016207:Cytokines; D016898:Interferon-alpha; D054380:Receptors, CXCR5; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
keywords: B cells; Cytokines; Hepatitis C virus; Interferon; PD-1; T follicular helper cells