Hoene Victoria, Peiser Matthias, Wanner Reinhard
Institute of Molecular Biology and Bioinformatics, Charité-CBF, Arnimallee 22, 14195 Berlin, Germany.
J Leukoc Biol. 2006 Dec;80(6):1328-36. doi: 10.1189/jlb.0106011. Epub 2006 Sep 25.
Oligodeoxynucleotides (ODNs) containing unmethylated CpG exhibit their immunostimulatory activities by binding to TLR. Here, we show that human monocyte-derived dendritic cells (moDC) contain TLR9 protein, surprisingly, in amounts comparable with plasmacytoid DC (pDC). Immature moDC but not mature moDC nor monocytes captured CpG-ODNs. moDC stimulation with the CpG-A ODN D19 up-regulated CD83, CD86, and HLA-DR. Without CD40 ligand costimulation, full maturation was not achieved. D19-stimulated moDC primed allogeneic CD4(+)-T cells for proliferation and differentiation into IFN-gamma-secreting Th1 cells. Neither IL-12 nor IL-6 or TNF-alpha was involved. Microarray analysis pointed to a participation of Type I IFNs. In fact, D19-stimulated moDC secreted considerable amounts of IFN-alpha. This indicates that moDC themselves sense viral and bacterial DNA and do not need help from pDC.
含有未甲基化CpG的寡脱氧核苷酸（ODN）通过与Toll样受体（TLR）结合发挥其免疫刺激活性。在此，我们发现人单核细胞来源的树突状细胞（moDC）含有TLR9蛋白，令人惊讶的是，其含量与浆细胞样树突状细胞（pDC）相当。未成熟的moDC而非成熟的moDC或单核细胞能够摄取CpG-ODN。用CpG-A ODN D19刺激moDC可上调CD83、CD86和HLA-DR的表达。在没有CD40配体共刺激的情况下，无法实现完全成熟。D19刺激的moDC启动同种异体CD4(+) -T细胞增殖并分化为分泌IFN-γ的Th1细胞。这一过程与IL-12、IL-6或TNF-α均无关。微阵列分析表明I型干扰素参与其中。事实上，D19刺激的moDC分泌大量的IFN-α。这表明moDC自身能够识别病毒和细菌DNA且不需要pDC的协助。
