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Immunotherapy with a recombinant hybrid molecule alleviates allergic responses more efficiently than an allergenic cocktail or pollen extract in a model of Chenopodium album allergy

机译:重组杂合分子的免疫疗法比藜芦蛋白过敏模型中的过敏性鸡尾酒或花粉提取物更有效地缓解了过敏反应

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Background: The aim of this study is to assess the therapeutic potential of a recombinant hybrid molecule (rHM) alongside an allergenic cocktail from recombinant wild-type allergens as well as pollen extract on Chenopodium album allergy, using a BALB/c mouse model. Methods: The BALB/c mice had already been sensitized to C. album via intraperitoneal injections of alum-adsorbed allergenic cocktail and immunotherapy procedure was followed by subcutaneous injections of the rHM, allergenic cocktail and pollen extract at weekly intervals. Humoral immune responses were determined via measurement of specific antibodies in serum. Splenocytes of immunized mice were stimulated in vitro and then proliferation responses, cytokine secretion and mRNA expression of genes involved in immunotherapy were examined by ELISA and real-time PCR. Results: Sensitized mice were identified with high specific IgE against allergenic cocktail when compared with healthy mice. Immunotherapy with the rHM induced the highest ratio of the IgG2a/IgG1 levels compared to allergenic cocktail or C. album pollen extract. The rHM was able to induce proliferative responses as well as the allergenic cocktail in cultured splenocytes. Immunotherapy with the rHM significantly improved secretion of IFN-γ and IL-10, while secretion of IL-13 rapidly diminished. Interestingly, mRNA expression of GATA3 was strongly decreased in rHM-treated mice whereas mRNA expression of T-bet and Foxp3 was significantly increased. Conclusion: Our results prove that immunotherapy with the rHM effectively controlled allergic responses by shifting from a Th2-like immune response to a Th1-dominated immune response.
机译:背景:本研究的目的是使用BALB / c小鼠模型评估重组杂种分子(rHM)与重组野生型变应原的变应原性混合物以及花粉提取物对藜属白粉病的治疗潜力。方法:已经通过腹膜内注射明矾吸附的致敏混合物对BALB / c小鼠致敏了C. Albumin,并通过免疫疗法随后每周一次皮下注射rHM,致敏混合物和花粉提取物。通过测量血清中的特异性抗体来确定体液免疫反应。在体外刺激免疫小鼠的脾细胞,然后通过ELISA和实时PCR检测参与免疫治疗的基因的增殖反应,细胞因子分泌和mRNA表达。结果:与健康小鼠相比,鉴定出的致敏小鼠具有针对过敏性鸡尾酒的高特异性IgE。与过敏性鸡尾酒或C. album花粉提取物相比,rHM免疫疗法诱导的IgG2a / IgG1水平比例最高。 rHM能够在培养的脾细胞中诱导增殖反应以及变应原性混合物。用rHM进行的免疫疗法可显着改善IFN-γ和IL-10的分泌,而IL-13的分泌则迅速减少。有趣的是,在rHM处理的小鼠中GATA3的mRNA表达大大降低,而T-bet和Foxp3的mRNA表达则明显增加。结论:我们的结果证明,使用rHM的免疫疗法可从类似Th2的免疫反应转变为以Th1为主的免疫反应,从而有效地控制了过敏反应。

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