These authors contributed equally to the study.
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
Article first published online: 19 AUG 2013
Copyright © 2013 by the American Association for the Study of Liver Diseases
Volume 58, Issue 4, pages 1277–1286, October 2013
How to Cite
Li, Y., Ma, S., Tang, L., Li, Y., Wang, W., Huang, X., Lai, Q., Zhang, M., Sun, J., Li, C. K., Abbott, W. G.H., Naoumov, N. V., Zhang, Y. and Hou, J. (2013), 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. Hepatology, 58: 1277–1286. doi: 10.1002/hep.26489
Potential conflict of interest: J.L.H. is on the speakers' bureau of, and has received research support grants from, Bristol-Myers Squibb, Novartis, GlaxoSmithKline, and Roche. N.V.N. is an employee of Novartis.
This study was supported by grants from the Major Science and Technology Special Project of China (2012ZX10002-003 and 2011CB946100) and the Natural Science Foundation of China (30830091 and 81270025).
- Issue published online: 1 OCT 2013
- Article first published online: 19 AUG 2013
- Accepted manuscript online: 22 MAY 2013 10:46AM EST
- Manuscript Accepted: 17 APR 2013
- Manuscript Received: 8 DEC 2012
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. Conclusion: 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;58:1277–1286)