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HBcAg‐pulsed dendritic cell vaccine induces Th1 polarization and production of hepatitis B virus‐specific cytotoxic T lymphocytes
Author(s) -
Chen Weiwei,
Shi Ming,
Shi Feng,
Mao Yuanli,
Tang Zirong,
Zhang Bin,
Zhang Hui,
Chen Liangen,
Chen Liming,
Xin Shaojie,
Wang Fusheng
Publication year - 2009
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2008.00468.x
Subject(s) - hbcag , cytotoxic t cell , hepatitis b virus , antigen , hbsag , ctl* , immunology , cd8 , virology , medicine , immune system , biology , in vitro , virus , biochemistry
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.