{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T13:03:33Z","timestamp":1791896613244,"version":"4.3.4"},"reference-count":23,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":700,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2013,10]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>\n                                 <jats:bold>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 (<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>&lt; 0.001) and longitudinal (<\/jats:bold>\n                                 <jats:bold>\n                                    P =\n                                 <\/jats:bold>\n                                 <jats:bold>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 (<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 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 (<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.011). Of note, the increase in frequency of anti-HBe-secreting B cells was abrogated by soluble recombinant IL-21 receptor-Fc chimera (<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.027), whereas exogenous recombinant IL-21 enhanced this effect (<\/jats:bold>\n                                 <jats:bold>\n                                    P\n                                 <\/jats:bold>\n                                 <jats:bold>= 0.043). Additionally, circulating CXCR5+CD4+ T cells shared similar phenotypic markers, and were positively correlated in frequency with, splenic follicular T helper cells.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion\n                                 <\/jats:bold>\n                                 <jats:bold>: Circulating CXCR5+CD4+ T cells, by producing IL-21, may have a significant role in facilitating HBeAg seroconversion in patients with chronic HBV infection. (Hepatology 2013;58:1277\u20131286)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.26489","type":"journal-article","created":{"date-parts":[[2013,5,22]],"date-time":"2013-05-22T16:03:32Z","timestamp":1369238612000},"page":"1277-1286","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":82,"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 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