Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs
Regulation of T-helper type 2 cell and airway eosinophilia by transmucosal coadministration of antigen and oligodeoxynucleotides containing CpG motifs
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DOI：
10.1165/ajrcmb.22.2.3772
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发表时间：
2000-02-01
影响因子：
6.4
通讯作者：
Shirato, K
中科院分区：
文献类型：
--
作者：
Shirota, H;Sano, K;Shirato, K
支气管哮喘的特征。包括气道嗜酸性粒细胞增多和免疫球蛋白 (IE)E 水平升高，已知是由 T 辅助细胞 (Th) 2 细胞精心策划的。含有 CpG 基序 (CpG) 的寡脱氧核苷酸最近被强调作为一种免疫调节剂，偏向 Th1 主导表型，然而，CpG 可能会引起非特异性 Th1 激活和毒性作用。在这项研究中，我们报告了一种通过经粘膜接种抗原和 CpG、气管内滴注 CpG 来抑制 Th2 细胞的新方法。 抑制抗原致敏小鼠的气道嗜酸性粒细胞增多和 Th2 细胞因子的产生，在抗原攻击的同时或之前给予 CpG 时观察到抑制作用。值得注意的是，同时给予 CpG 和抗原（相对于单独使用其中任何一种）对于抑制作用至关重要。可以最大限度地减少抗原剂量，以避免有害的嗜酸性粒细胞增多，CpG 对全身抗卵清蛋白 IEE 反应几乎没有影响。这些结果表明，经粘膜施用的过敏原和 CpG 之间的协同作用可同时抑制 Th2 细胞，同时抑制 Th2 细胞。 改善气道嗜酸性粒细胞增多和高反应性，而不妨碍全身免疫反应。我们的数据表明，吸入最少量的过敏原加 CpG 可能是支气管哮喘患者的一种新型脱敏疗法。
The characteristic features of bronchial asthma. including airway eosinophilia and elevated immunoglobulin (IE)E levels, are known to be orchestrated by T-helper (Th) 2 cells. Oligodeoxynucleotides containing CpG motifs (CpG) have recently been highlighted as an immunomodulator that biases toward a Th1-dominant phenotype, However, CpG may incur nonspecific Th1 activation and toxic effects, In this study we report a novel inhibition of Th2 cells by transmucosal inoculation of antigen and CpG, Intratracheal instillation of CpG inhibited airway eosinophilia and Th2 cytokine production in antigen-sensitized mice, The inhibition was observed when CpG was given at the same time or in advance of antigen challenge. Notably, concomitant administration of CpG and antigen las opposed to either one alone) was essential for the inhibitory effects, The antigen dose could be minimized to avoid a harmful boost of eosinophilia, CpG had few effects on systemic anti-ovalbumin IEE responses, These results demonstrate that a synergism between transmucosally administered allergen and CpG inhibits Th2 cells in parallel with an improvement in airway eosinophilia and hyperresponsiveness without impeding systemic immune responses. Our data imply that inhalation of a minimal amount of allergen plus CpG could be a novel desensitization therapy for patients with bronchial asthma.