title: Circulating chemokine (C-X-C Motif) receptor 5(+) CD4(+) T cells benefit hepatitis B e antigen seroconversion through IL-21 in patients with chronic hepatitis B virus infection.
abstract: Given the clinical significance of hepatitis B e antigen (HBeAg) seroconversion in chronic hepatitis B virus (HBV) infection, it is critical to elucidate the mechanisms regulating this process. In the present study, we found that the frequency of circulating chemokine (C-X-C motif) receptor 5 (CXCR5)(+) CD4(+) T cells was higher in patients who had achieved HBeAg seroconversion in both cross-sectional (P < 0.001) and longitudinal (P = 0.009) studies. These cells were able to produce a significantly higher level of intracellular interleukin 21 (IL-21) after stimulation with HBV peptides in patients with telbivudine-induced HBeAg seroconversion (P = 0.007). Furthermore, sorted CXCR5(+) CD4(+) T cells from HBeAg seroconverters boosted a higher frequency of antibody against hepatitis B e antigen (anti-HBe)-secreting B cells in coculture assay (P = 0.011). Of note, the increase in frequency of anti-HBe-secreting B cells was abrogated by soluble recombinant IL-21 receptor-Fc chimera (P = 0.027), whereas exogenous recombinant IL-21 enhanced this effect (P = 0.043). Additionally, circulating CXCR5(+) CD4(+) T cells shared similar phenotypic markers, and were positively correlated in frequency with, splenic follicular T helper cells.
  
  
  CONCLUSIONS
  Circulating CXCR5(+) CD4(+) T cells, by producing IL-21, may have a significant role in facilitating HBeAg seroconversion in patients with chronic HBV infection.
authors.affiliation: Department of Infectious Diseases and Hepatology Unit, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yongyin
authors.initials: Y
authors.lastname: Li
authors.forename: Shiwu
authors.initials: S
authors.lastname: Ma
authors.forename: Libo
authors.initials: L
authors.lastname: Tang
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Xuan
authors.initials: X
authors.lastname: Huang
authors.forename: Qintao
authors.initials: Q
authors.lastname: Lai
authors.forename: Mingxia
authors.initials: M
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.forename: Chris Kafai
authors.initials: CK
authors.lastname: Li
authors.forename: William G H
authors.initials: WG
authors.lastname: Abbott
authors.forename: Nikolai V
authors.initials: NV
authors.lastname: Naoumov
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinlin
authors.initials: J
authors.lastname: Hou
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000276:immunology; D019694:Hepatitis B, Chronic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007378:Interleukins / Q000378:metabolism* / Q000494:pharmacology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D054380:Receptors, CXCR5 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000494:pharmacology; D000077712:Telbivudine; D013936:Thymidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D000914:Antibodies, Viral; D000998:Antiviral Agents; D015415:Biomarkers; C095085:CXCR5 protein, human; D006513:Hepatitis B e Antigens; D007378:Interleukins; D054380:Receptors, CXCR5; D011994:Recombinant Proteins; D000077712:Telbivudine; D000098546:Interleukin-21; D013936:Thymidine