Rothenfusser Simon, Tuma Evelyn, Endres Stefan, Hartmann Gunther
Department of Internal Medicine, Division of Clinical Pharmacology, University of Munich, Munich, Germany.
Hum Immunol. 2002 Dec;63(12):1111-9. doi: 10.1016/s0198-8859(02)00749-8.
The vertebrate immune system has established TLR9 to detect microbial DNA based on unmethylated CG dinucleotides within certain sequence contexts (CpG motifs). In humans, the expression of toll-like receptor 9 (TLR9) is restricted to B cells and plasmacytoid dendritic cells (PDC). The PDC is characterized by the ability to rapidly synthesize large amounts of type I IFN (IFN-alpha and IFN-beta) in response to viral infection. In contrast to other dendritic cell subsets which express a broad profile of TLRs, the TLR profile in PDC is restricted to TLR7 and TLR9. So far, CpG DNA is the only defined microbial molecule recognized by PDC. An intriguing feature of PDC is its ability to simultaneously produce the two major Th1-inducing cytokines in humans, IFN-alpha and IL-12, both at high levels. The ratio of IFN-alpha versus IL-12 and the quantity of these cytokines are regulated by T helper cell-mediated costimulation via CD40 ligation. The ratio also depends on the differentiation stage of the PDC at the time of stimulation and the type of CpG ODN used. We propose a model in which the establishment of Th1 responses in vivo is improved by appropriately stimulated PDC that otherwise - in the absence of CpG DNA--support Th2 or Th0 responses and thus have been called DC2.
脊椎动物免疫系统已建立起Toll样受体9（TLR9），以便在特定序列背景（CpG基序）下基于未甲基化的CG二核苷酸来检测微生物DNA。在人类中，Toll样受体9（TLR9）的表达仅限于B细胞和浆细胞样树突状细胞（pDC）。pDC的特点是能够在病毒感染后迅速合成大量I型干扰素（IFN-α和IFN-β）。与表达多种TLR的其他树突状细胞亚群不同，pDC中的TLR谱仅限于TLR7和TLR9。到目前为止，CpG DNA是pDC识别的唯一已明确的微生物分子。pDC的一个有趣特征是其能够同时高水平产生人类中两种主要的Th1诱导细胞因子，即IFN-α和IL-12。IFN-α与IL-12的比例以及这些细胞因子的量受T辅助细胞通过CD40连接介导的共刺激调节。该比例还取决于刺激时pDC的分化阶段以及所用CpG ODN的类型。我们提出了一个模型，其中体内Th1反应的建立通过适当刺激的pDC得到改善，否则在没有CpG DNA的情况下，pDC会支持Th2或Th0反应，因此被称为DC2。
