Vaccination with plasmid DNA activates dendritic cells via toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice
Vaccination with plasmid DNA activates dendritic cells via toll-like receptor 9 (TLR9) but functions in TLR9-deficient mice
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DOI：
10.4049/jimmunol.171.11.5908
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发表时间：
2003-12-01
影响因子：
4.4
通讯作者：
Wagner, H
中科院分区：
文献类型：
--
作者：
Spies, B;Hochrein, H;Wagner, H
我们分析了接种含有OVA转录单位的质粒DNA的免疫生物学是否受到质粒主干中免疫刺激CpG基序的影响。事实上，质粒DNA在体外骨髓和浆细胞样树突状细胞（DCs）中被差异激活，前提是它们表达CpG-DNA受体toll样受体9 （TLR9）。依赖于DC亚群，激活导致1型IFN产生，而DC亚群产生IL-6并上调共刺激分子CD40和CD86的表达。然而，在体内，即使用质粒DNA反复接种，在TLR9阳性和TLR9-或myd88阴性小鼠中，ova特异性CTL的引物和siinfekl特异性CD8 T细胞的克隆扩增是相同的。总的来说，这些结果否定了CpG-DNA/TLR9相互作用在长期疫苗接种方案中的主导作用。
We analyzed whether the immunobiology of vaccinating plasmid DNA containing a transcription unit for OVA is influenced by immunostimulatory CpG motifs in the plasmid backbone. Indeed, plasmid DNA differentially activated in vitro myeloid and plasmacytoid dendritic cells (DCs) provided they expressed the CpG-DNA receptor, Toll-like receptor 9 (TLR9). Dependent on the DC subset, activation resulted in type 1 IFN production, while both DC subsets produced IL-6 and up-regulated expression of costimulatory molecules CD40 and CD86. In vivo, however, even upon repeated vaccination with plasmid DNA, priming of OVA-specific CTL and clonal expansion of SIINFEKL-specific CD8 T cells were equal in TLR9-positive and TLR9- or MyD88-negative mice. Overall, these results negate a dominant role of CpG-DNA/TLR9 interactions in long-term vaccination protocols.