CpG DNA: a potent signal for growth, activation, and maturation of human dendritic cells.
TLDR
In this paper, the effects of CpG oligodeoxynucleotides alone or in combination with granulocyte-macrophage colony-stimulating factor (GMCSF) on different classes of purified human Dendritic cells (DCs) were evaluated.Abstract:
DNA molecules containing unmethylated CpG-dinucleotides in particular base contexts ("CpG motifs") are excellent adjuvants in rodents, but their effects on human cells have been less clear. Dendritic cells (DCs) form the link between the innate and the acquired immune system and may influence the balance between T helper 1 (Th1) and Th2 immune responses. We evaluated the effects of CpG oligodeoxynucleotides alone or in combination with granulocyte-macrophage colony-stimulating factor (GMCSF) on different classes of purified human DCs. For primary dendritic precursor cells isolated from human blood, CpG oligonucleotides alone were superior to GMCSF in promoting survival and maturation (CD83 expression) as well as expression of class II MHC and the costimulatory molecules CD40, CD54, and CD86 of DCs. Both CD4-positive and CD4-negative peripheral blood dendritic precursor cells responded to CpG DNA which synergized with GMCSF but these DCs showed little response to lipopolysaccharide (LPS). In contrast, monocyte-derived DCs did not respond to CpG, but they were highly sensitive to LPS, suggesting an inverse correlation between CpG and LPS sensitivity in different subsets of DCs. Compared with GMCSF, CpG-treated peripheral blood DCs showed enhanced functional activity in the mixed lymphocyte reaction and induced T cells to secrete increased levels of Th1 cytokines. These findings demonstrate the ability of specific CpG motifs to strongly activate certain subsets of human DCs to promote Th1-like immune responses, and support the use of CpG DNA-based trials for immunotherapy against cancer, allergy, and infectious diseases.read more
Citations
More filters
Journal ArticleDOI
Immunobiology of Dendritic Cells
Jacques Banchereau,Francine Brière,Christophe Caux,Jean Davoust,Serge Lebecque,Yong-Jun Liu,Bali Pulendran,Karolina Palucka +7 more
TL;DR: Dendritic cells are antigen-presenting cells with a unique ability to induce primary immune responses and may be important for the induction of immunological tolerance, as well as for the regulation of the type of T cell-mediated immune response.
Journal ArticleDOI
A Toll-like receptor recognizes bacterial DNA.
Hiroaki Hemmi,Osamu Takeuchi,Taro Kawai,Tsuneyasu Kaisho,Shintaro Sato,Hideki Sanjo,Makoto Matsumoto,Katsuaki Hoshino,Hermann Wagner,Kiyoshi Takeda,Shizuo Akira +10 more
TL;DR: It is shown that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9, and vertebrate immune systems appear to have evolved a specific Toll- like receptor that distinguishes bacterial DNA from self-DNA.
Journal ArticleDOI
CpG Motifs in Bacterial DNA and Their Immune Effects
TL;DR: Oligodeoxynucleotides containing CpG ODN enhance the development of acquired immune responses for prophylactic and therapeutic vaccination and protect against lethal challenge with a wide variety of pathogens.
Journal ArticleDOI
Mouse and human dendritic cell subtypes
Ken Shortman,Yong-Jun Liu +1 more
TL;DR: The dynamics of the DC network in response to microbial invasion is studied, because many DC subtypes arise from separate developmental pathways, and their development and function are modulated by exogenous factors.
Journal ArticleDOI
Quantitative Expression of Toll-Like Receptor 1–10 mRNA in Cellular Subsets of Human Peripheral Blood Mononuclear Cells and Sensitivity to CpG Oligodeoxynucleotides
Veit Hornung,Simon Rothenfusser,Stefanie Britsch,Anne Krug,Bernd Jahrsdörfer,Thomas Giese,Stefan Endres,Gunther Hartmann +7 more
TL;DR: Evidence is provided that PDC and B cells, but not monocytes, NK cells, or T cells, are primary targets of CpG ODN in peripheral blood.
References
More filters
Journal ArticleDOI
Cpg motifs in bacterial dna trigger direct b-cell activation
Arthur M. Krieg,Ae-Kyung Yi,Sara Matson,Thomas J. Waldschmidt,Gail A. Bishop,Gail A. Bishop,Rebecca M. Teasdale,Gary A. Koretzky,Dennis M. Klinman +8 more
TL;DR: The potent immune activation by CpG oligon nucleotides has impli-cations for the design and interpretation of studies using 'antisense' oligonucleotides and points to possible new applications as adjuvants.
Journal ArticleDOI
Vaccination of melanoma patients with peptide- or tumor lysate-pulsed dendritic cells.
Frank O. Nestle,Selma Alijagic,Michel Gilliet,Yuansheng Sun,Stephan Grabbe,Reinhard Dummer,Günter Burg,Dirk Schadendorf +7 more
TL;DR: Vaccination with autologous DCs generated from peripheral blood is a safe and promising approach in the treatment of metastatic melanoma and antigen-specific immunity was induced during DC vaccination.
Journal ArticleDOI
T-cell help for cytotoxic T lymphocytes is mediated by CD40–CD40L interactions
Stephen P. Schoenberger,René E. M. Toes,E.I.H. van der Voort,R. Offringa,Cornelis J. M. Melief +4 more
TL;DR: In this paper, it was shown that signalling through CD40 can replace CD4+ T-helper cells in priming of helper-dependent CD8+ CTL responses.
Journal ArticleDOI
A conditioned dendritic cell can be a temporal bridge between a CD4 + T-helper and a T-killer cell
TL;DR: It is found that the three cells need not meet simultaneously but that the helper cell can first engage and ‘condition’ the dendritic cell, which then becomes empowered to stimulate a killer cell.
Journal ArticleDOI
Help for cytotoxic-T-cell responses is mediated by CD40 signalling
Sally R.M. Bennett,Sally R.M. Bennett,Francis R. Carbone,Freda Karamalis,Freda Karamalis,Richard A. Flavell,Jacques F. A. P. Miller,William R. Heath +7 more
TL;DR: It is shown that signalling through CD40 on the antigen-presenting cells can replace the requirement for TH cells, indicating that T-cell ‘help’, at least for generation of CTLs by cross-priming, is mediated by signalling throughCD40 onThe antigen- presenting cell.