Jakob T, Walker P S, Krieg A M, Udey M C, Vogel J C
Dermatology Branch, National Cancer Institute, Bethesda, MD 20892-1908, USA.
J Immunol. 1998 Sep 15;161(6):3042-9.
Genetic vaccination depends at least in part on the adjuvant properties of plasmids, properties that have been ascribed to unmethylated CpG dinucleotides in bacterial DNA. Because dendritic cells (DC) participate in the T cell priming that occurs during genetic vaccination, we reasoned that CpG-containing DNA might activate DC. Thus, we assessed the effects of CpG oligodeoxynucleotides (CpG ODN) on Langerhans cell (LC)-like murine fetal skin-derived DC (FSDDC) in vitro and on LC in vivo. Treatment with CpG ODN as well as LPS induced FSDDC maturation, manifested by decreased E-cadherin-mediated adhesion, up-regulation of MHC class II and costimulator molecule expression, and acquisition of enhanced accessory cell activity. In contrast to LPS, CpG ODN stimulated FSDDC to produce large amounts of IL-12 but only small amounts of IL-6 and TNF-alpha. Injection of CpG ODN into murine dermis also led to enhanced expression of MHC class II and CD86 Ag by LC in overlying epidermis and intracytoplasmic IL-12 accumulation in a subpopulation of activated LC. We conclude that immunostimulatory CpG ODN stimulate DC in vitro and in vivo. Bacterial DNA-based vaccines may preferentially elicit Th1-predominant immune responses because they activate and mobilize DC and induce them to produce large amounts of IL-12.
基因疫苗接种至少部分依赖于质粒的佐剂特性，这些特性归因于细菌DNA中未甲基化的CpG二核苷酸。由于树突状细胞（DC）参与基因疫苗接种过程中发生的T细胞启动，我们推测含CpG的DNA可能激活DC。因此，我们评估了CpG寡脱氧核苷酸（CpG ODN）对体外朗格汉斯细胞（LC）样小鼠胎儿皮肤来源的DC（FSDDC）以及体内LC的影响。用CpG ODN和LPS处理均可诱导FSDDC成熟，表现为E-钙黏蛋白介导的黏附减少、MHC II类分子和共刺激分子表达上调以及辅助细胞活性增强。与LPS不同，CpG ODN刺激FSDDC产生大量IL-12，但仅产生少量IL-6和TNF-α。将CpG ODN注射到小鼠真皮中还导致上层表皮中的LC增强表达MHC II类分子和CD86抗原，以及活化LC亚群中出现胞质内IL-12积累。我们得出结论，免疫刺激性CpG ODN在体外和体内均可刺激DC。基于细菌DNA的疫苗可能优先引发以Th1为主的免疫反应，因为它们激活并动员DC，并诱导它们产生大量IL-12。
