Activated plasmacytoid dendritic cells act synergistically with hepatitis B core antigen-pulsed monocyte-derived dendritic cells in the induction of hepatitis B virus-specific CD8 T-cell response.
It is important to further improve the efficiency of hepatitis B core antigen-pulsed monocyte-derived dendritic cell (core-DC) vaccine in clinical immunotherapy for chronic hepatitis B virus (HBV) infection in humans. Our study shows that CpG-treated plasmacytoid dendritic cells (pDCs) can efficiently promote core-DC terminal maturation and increase interleukin-12 production. These CpG-activated pDCs can act synergistically in vitro with core-DCs in inducing autologous HBV-specific CD8 T-cell proliferation and interferon (IFN)-gamma production. This promotion was mainly dependent on pDC-derived IFN-alpha, because blockade of IFN-alpha nearly completely aborted the effects of pDCs on core-DCs. In addition, the supernatants derived from CpG-treated peripheral blood mononuclear cells can also effectively improve the aforementioned maturation and function of core-DCs. These findings will facilitate a better understanding of how the pDCs regulate myeloid dendritic cell-mediated immune responses, and highlight the notion that manipulating pDCs might have implications in DC vaccine therapy for patients with chronic hepatitis B.
Chen
Weiwei
W
Research Center for Biological Therapy, Beijing 302 Hospital, Beijing 100039, China.
Zhang
Zheng
Z
Shi
Ming
M
Chen
Liangen
L
Fu
Junliang
J
Shi
Feng
F
Zhang
Bing
B
Zhang
Hui
H
Jin
Lei
L
Wang
Fu-Sheng
FS
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006512:Hepatitis B Core Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000628:therapy; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C408982:CPG-oligonucleotide; D006512:Hepatitis B Core Antigens; D016898:Interferon-alpha; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma