IPP-Department of Pathophysiology, Center of Physiology, Pathophysiology and Immunology, Medical University of Vienna, Austria.
Clin Exp Allergy. 2010 Apr;40(4):650-8. doi: 10.1111/j.1365-2222.2009.03392.x. Epub 2009 Dec 2.
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.
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.
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.
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.
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.
变应原特异性免疫治疗的一个关注点是炎症性变应原特异性 T 淋巴细胞的可能增强。为了解决这个问题，用不含变应原特异性 T 细胞表位的 B 细胞表位进行治疗将是一种很有前途的选择。
在这项研究中，我们研究了一个单一模拟表位的治疗效果，该模拟表位模拟了草花粉过敏原 Phl p 5 的一个结构 IgE 表位，在一个已建立的急性过敏性哮喘的记忆小鼠模型中。
在实验设置中，BALB/c 小鼠用重组 Phl p 5a(rPhl p 5a)经腹腔注射进行致敏，然后用雾化过敏原进行气溶胶挑战。小鼠出现了支气管哮喘的症状，包括支气管周围嗜酸性粒细胞增多、杯状细胞增生和黏液分泌增加。
当小鼠随后用与血蓝蛋白偶联的草花粉模拟表位进行治疗时，支气管嗜酸性粒细胞炎症和黏液分泌过度减少。此外，在支气管肺泡灌洗液（BAL）中可以观察到 Th2 细胞因子 IL-4 和 IL-5 的减少。与 rPhl p 5a 相反，该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 水平，但用单一模拟表位进行疫苗接种在急性哮喘的小鼠模型中产生了抗炎作用。
从我们的数据中，我们得出结论，用代表过敏原 Phl p 5a 的单个 IgE 表位的模拟表位肽进行疫苗接种，并且不含变应原特异性 T 细胞表位，能够下调急性哮喘中的炎症。
