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Mimotope vaccination for therapy of allergic asthma: anti-inflammatory effects in a mouse model.

机译:用于治疗过敏性哮喘的模拟表位疫苗:在小鼠模型中的抗炎作用。

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BACKGROUND: One of the concerns of allergen-specific immunotherapy is the possible boost of inflammatory allergen-specific T lymphocytes. To address this problem, treatment with B cell epitopes devoid of allergen-specific T cell epitopes would be a promising alternative. OBJECTIVE: In this study, we examined the therapeutic potency of a single mimotope, mimicking a structural IgE epitope of grass pollen allergen Phl p 5 in an established memory mouse model of acute allergic asthma. METHODS: In the experimental set-up, BALB/c mice were primed with intraperitoneal injections of recombinant Phl p 5a (rPhl p 5a) and subsequently aerosol challenged with the nebulized allergen. Mice developed signs of bronchial asthma including hypereosinophilia around bronchi, goblet cell hyperplasia and enhanced mucus production. RESULTS: When the mice were subsequently treated with the grass pollen mimotope coupled to keyhole limpet haemocyanin, bronchial eosinophilic inflammation and mucus hypersecretion decreased. Further, a decrease of Th2 cytokines IL-4 and IL-5 could be observed in the bronchoalveolar lavage (BAL). In contrast to rPhl p 5a, the mimotope was in vitro not able to stimulate splenocytes to proliferation or IL-5 production. Despite not affecting the levels of pre-existing IgE, vaccination with the single mimotope thus rendered anti-inflammatory effects in a mouse model of acute asthma. CONCLUSION: From our data, we conclude that vaccination with a mimotope peptide representing a single IgE epitope of the allergen Phl p 5a and being devoid of allergen-specific T cell epitopes is able to down-regulate inflammation in acute asthma.
机译:背景:过敏原特异性免疫治疗的关注之一是可能增加炎症性过敏原特异性T淋巴细胞。为了解决这个问题,用不含过敏原特异性T细胞表位的B细胞表位进行治疗将是有前途的选择。目的:在这项研究中,我们检查了单个拟表位的治疗效力,该模型模仿了已建立的急性过敏性哮喘小鼠模型中的花粉过敏原Phl p 5的结构性IgE表位。方法:在实验设置中,将BALB / c小鼠腹膜内注射重组Phl p 5a(rPhl p 5a)引发,然后用雾化的过敏原进行气雾攻击。小鼠出现支气管哮喘的体征,包括支气管周围的嗜酸性粒细胞增多,杯状细胞增生和粘液产生增加。结果:当随后对小鼠用草花粉模拟表位结合匙孔血蓝蛋白治疗时,支气管嗜酸性炎症和粘液过度分泌减少。此外,在支气管肺泡灌洗(BAL)中可观察到Th2细胞因子IL-4和IL-5的减少。与rPhl p 5a相反,模拟表位在体外不能刺激脾细胞增殖或产生IL-5。尽管不影响预​​先存在的IgE的水平,但单一模拟表位的疫苗接种因此在急性哮喘的小鼠模型中具有抗炎作用。结论:根据我们的数据,我们得出结论,用代表变应原Phl p 5a的单个IgE表位并且不含变应原特异性T细胞表位的模拟表位疫苗接种能够下调急性哮喘的炎症反应。

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