Weiwei Chen and Ming Shi contributed equally to this study.
HBcAg-pulsed dendritic cell vaccine induces Th1 polarization and production of hepatitis B virus-specific cytotoxic T lymphocytes
Article first published online: 30 DEC 2008
© 2008 The Japan Society of Hepatology
Volume 39, Issue 4, pages 355–365, April 2009
How to Cite
Chen, W., Shi, M., Shi, F., Mao, Y., Tang, Z., Zhang, B., Zhang, H., Chen, L., Chen, L., Xin, S. and Wang, F.-s. (2009), HBcAg-pulsed dendritic cell vaccine induces Th1 polarization and production of hepatitis B virus-specific cytotoxic T lymphocytes. Hepatology Research, 39: 355–365. doi: 10.1111/j.1872-034X.2008.00468.x
- Issue published online: 26 MAR 2009
- Article first published online: 30 DEC 2008
- Received 19 June 2008; revised 17 September 2008; accepted 21 October 2008.
- chronic hepatitis B;
- dendritic cells;
- hepatitis B virus;
- T helper cell
Aim: Dendritic cells (DCs) pulsed with HBsAg efficiently reverse the immune tolerance to hepatitis B virus (HBV) and induce HBV-specific cytotoxic T lymphocyte (CTL) responses in transgenic mice and healthy volunteers. However, it is not clear whether HBV core antigen (HBcAg)-pulsed DCs can effectively induce CD4+ helper T cells polarization into Th1, which contribute to the induction and maintenance of HBV-specific CD8+ T cells in chronic hepatitis B (CHB) patients. To address this issue, we conducted this study and investigated whether HBcAg-pulsed DCs could polarize Th1 cells and induce an HBcAg-specific CTL response.
Methods: HBcAg-pulsed DCs were generated from 21 CHB patients. The capacity of the HBcAg-pulsed DC vaccine to stimulate CD4+ and CD8+ T cells to produce IFN-γ and IL-4 was estimated by intercellular cytokine staining, and the HBcAg-pulsed DCs derived from 10 humam leucocyte antigen (HLA)-A2+ CHB patients were tested for the induction of HBV-specific CTLs from autologous T cells by pentamer staining. The cytotoxicity of these CTLs was evaluated in vitro by flow cytometry.
Results: The HBcAg-pulsed DCs derived from CHB patients exhibited a stronger capacity to stimulate autologous CD4+ and CD8+ T cells to release IFN-γ rather than IL-4, which could induce HBV core 18-27 specific CTLs, suggesting a specific cytotoxicity against T2 cells that had been loaded with the HBV core 18-27 peptide in vitro.
Conclusion: HBcAg-pulsed DC vaccine derived from CHB patients efficiently induced autologous T cell polarization to Th1 and generation of HBV core 18-27 specific CTLs.