Zimmermann S, Egeter O, Hausmann S, Lipford G B, Röcken M, Wagner H, Heeg K
Institute of Medical Microbiology, Immunology and Hygiene, Technische Universität München, Germany.
J Immunol. 1998 Apr 15;160(8):3627-30.
Synthetic oligodeoxynucleotides containing CpG dinucleotides (CpG-ODN) mimic the immunostimulatory qualities of bacterial DNA. We asked whether immunostimulation by CpG-ODN predisposes for a commitment toward a Th1 vs a Th2 response in Leishmania major infection, a model for a lethal Th2-driven disease, in BALB/c mice. CpG-ODN induced Th1 effector T cells in vitro and conveyed protective immunity to disease-prone BALB/c mice in vivo. Conversion to a Th1-driven resistant phenotype was associated with IL-12 production and maintained the expression of IL-12R beta2-chains. Most strikingly, CpG-ODN were even curative when given as late as 20 days after lethal L. major infection, indicating that CpG-ODN revert an established Th2 response. These findings imply an important role of bacterial DNA and CpG-ODN in the instruction of adaptive immune responses. They also point to the therapeutic potential of CpG-ODN in redirecting curative Th1 responses in Th2-driven disorders.
含有CpG二核苷酸的合成寡脱氧核苷酸（CpG-ODN）模拟细菌DNA的免疫刺激特性。我们研究了在利什曼原虫主要感染（一种由Th2驱动的致死性疾病模型）中，CpG-ODN诱导的免疫刺激是否会使BALB/c小鼠倾向于向Th1或Th2反应发展。CpG-ODN在体外诱导Th1效应T细胞，并在体内向易患疾病的BALB/c小鼠传递保护性免疫。向Th1驱动的抗性表型的转变与IL-12的产生相关，并维持IL-12Rβ2链的表达。最引人注目的是，即使在致死性利什曼原虫主要感染后20天给予CpG-ODN，它仍具有治疗作用，这表明CpG-ODN可逆转已建立的Th2反应。这些发现暗示细菌DNA和CpG-ODN在适应性免疫反应的指导中具有重要作用。它们还指出了CpG-ODN在Th2驱动的疾病中重定向治疗性Th1反应的治疗潜力。
