Kline J N, Waldschmidt T J, Businga T R, Lemish J E, Weinstock J V, Thorne P S, Krieg A M
Department of Medicine, University of Iowa College of Medicine, Iowa City 52242, USA.
J Immunol. 1998 Mar 15;160(6):2555-9.
Asthma has been increasing in industrialized countries. Evidence suggests that asthma is caused by a Th2 immune response to inhaled environmental Ags and that childhood infections protect against this. We have shown that bacterial DNA contains motifs, centered on unmethylated CpG dinucleotides, which induce Th1-type responses. We hypothesized that the Th1 effect of these CpG motifs may oppose the Th2 type allergic response and suggest that this may account for the protective effect of childhood infection against asthma. We examined the effects of CpG-motif oligodeoxynucleotides (CpG ODN) in a murine model of asthma. Airway eosinophilia, Th2 cytokine induction, IgE production, and bronchial hyperreactivity were prevented by coadministration of CpG ODN with the Ag. Significantly, in a previously sensitized mouse, CpG ODN can prevent allergen-induced airway inflammation. These studies suggest that exposure to CpG DNA may protect against asthma.
在工业化国家,哮喘发病率一直在上升。有证据表明,哮喘是由对吸入性环境抗原的Th2免疫反应引起的,而儿童期感染可预防哮喘。我们已经证明,细菌DNA含有以未甲基化的CpG二核苷酸为中心的基序,可诱导Th1型反应。我们推测,这些CpG基序的Th1效应可能会对抗Th2型过敏反应,并表明这可能解释了儿童期感染对哮喘的保护作用。我们在哮喘小鼠模型中研究了CpG基序寡脱氧核苷酸(CpG ODN)的作用。通过将CpG ODN与抗原共同给药,可预防气道嗜酸性粒细胞增多、Th2细胞因子诱导、IgE产生和支气管高反应性。重要的是,在先前致敏的小鼠中,CpG ODN可预防变应原诱导的气道炎症。这些研究表明,接触CpG DNA可能预防哮喘。