Schattenberg D, Schott M, Reindl G, Krueger T, Tschoepe D, Feldkamp J, Scherbaum W A, Seissler J
German Diabetes Research Institute, University of Düsseldorf.
Eur J Immunol. 2000 Oct;30(10):2824-31. doi: 10.1002/1521-4141(200010)30:10<2824::AID-IMMU2824>3.0.CO;2-3.
Activated dendritic cells (DC) are of key importance for the initiation of primary immune responses and represent promising tools for immunotherapies in humans. Since DNA containing CpG motifs have been described as potent immunostimulatory (IS) adjuvants for murine DC, we here studied maturation and stimulation of functional activity in human monocyte-derived DC (MODC) in response to several immunostimulatory oligodeoxynucleotides (IS-ODN) and plasmid DNA (IS-PL). We show that exposure of MODC to IS-PL, but not IS-ODN, induced a dose-dependent strong up-regulation of HLA class II and co-stimulatory molecules (CD80, CD86), similar to that observed after treatment with TNF-alpha. Functional activity was assessed by the detection of increased secretions of IL-6 and IL-12(p75) following treatment with IS-PL. In addition, IS-PL-stimulated MODC acquired a high T cell-stimulatory capacity. T cells stimulated by tetanus toxoid-pulsed, IS-PL-matured MODC were significantly more frequently IFN-gamma positive (25.2+/-2.7%) as compared to TNF-alpha-treated MODC (15.4+/-1.4%), indicating a strong activation of Th1 lymphocytes. In conclusion, we demonstrate that human MODC are activated by IS-PL but not IS-ODN previously used as adjuvants in animal models. The Th1-like immune response observed after stimulation with IS-PL-treated DC suggests that preincubation of human MODC with IS-PL or coimmunization with IS-PL may represent an useful approach to generate strongly activated human MODC for several therapeutic applications such as DC-based tumor immunotherapy.
活化的树突状细胞（DC）对于启动原发性免疫反应至关重要，是人类免疫治疗的有前景的工具。由于含CpG基序的DNA已被描述为小鼠DC的有效免疫刺激（IS）佐剂，我们在此研究了人类单核细胞衍生DC（MODC）对几种免疫刺激寡脱氧核苷酸（IS-ODN）和质粒DNA（IS-PL）的反应中功能活性的成熟和刺激。我们表明，MODC暴露于IS-PL而非IS-ODN会诱导HLA II类和共刺激分子（CD80、CD86）剂量依赖性的强烈上调，类似于用TNF-α处理后观察到的情况。通过检测IS-PL处理后IL-6和IL-12（p75）分泌增加来评估功能活性。此外，IS-PL刺激的MODC获得了高T细胞刺激能力。与TNF-α处理的MODC（15.4±1.4%）相比，破伤风类毒素脉冲、IS-PL成熟的MODC刺激的T细胞中IFN-γ阳性的频率显著更高（25.2±2.7%），表明Th1淋巴细胞被强烈激活。总之，我们证明人类MODC被IS-PL激活，但不被先前在动物模型中用作佐剂的IS-ODN激活。用IS-PL处理的DC刺激后观察到的Th1样免疫反应表明，用IS-PL预孵育人MODC或与IS-PL共同免疫可能是一种有用的方法，可为多种治疗应用（如基于DC的肿瘤免疫治疗）生成强活化的人类MODC。
