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粉尘螨变应原舌下免疫治疗对哮喘小鼠模型的疗效。

Sublingual immunotherapy efficacy of Dermatophagoides farinae vaccine in a murine asthma model.

机构信息

Allergy and Immunology Institute, Shenzhen University, Shenzhen, China.

出版信息

Int Arch Allergy Immunol. 2010;152(1):41-8. doi: 10.1159/000260082. Epub 2009 Nov 24.

Abstract

BACKGROUND

Allergen-specific sublingual immunotherapy is a potential treatment for allergic diseases. Its effective dose and underlying mechanism are still to be explored. Here, we investigated the efficacy and mechanism of sublingually administered Dermatophagoides farinae (Der f) vaccine in a murine asthma model.

METHODS

BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by sublingual treatment with Der f vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week. We analyzed their clinical symptoms, antibody levels, cytokine levels, T-cell proliferation and the regulatory T-cell numbers.

RESULTS

Mice treated with high-dose Der f sublingual vaccine prior to challenge displayed alleviated symptoms such as airway hyperreactivity, lung inflammation and mucus production, as well as less eosinophilic cells in bronchoalveolar lavage fluid. Interestingly, reduced responses of Der-f-specific IgE and increased responses of Der-f-specific IgA and IgG1 were aroused in the high-dose Der f sublingual vaccine group. We also observed that interleukin-4 was reduced and interferon-gamma and interleukin-10 were increased among splenocytes and in bronchoalveolar lavage fluid, which inhibited Der-f-specific T-cell proliferation of the spleen and increased CD4+CD25+Foxp3+regulatory T cells in the spleen. However, mice treated with low-dose Der f sublingual vaccine developed allergic asthma.

CONCLUSION

Our results illustrate that high-dose Der f sublingual vaccine may play a role in immunologic protection in murine allergic asthma, possibly by inducing regulatory T cells and Th1 reaction.

摘要

背景

变应原特异性舌下免疫疗法是治疗过敏性疾病的一种潜在方法。其有效剂量和潜在机制仍有待探索。在这里,我们研究了变应原特异性粉尘螨(Der f)疫苗经舌下给药在小鼠哮喘模型中的疗效和机制。

方法

BALB/c 小鼠经腹腔内用 Der f 提取物与明矾吸收致敏,随后用 Der f 疫苗经舌下给药 6 周。随后,用 Der f 提取物对小鼠进行鼻内攻击 1 周。我们分析了它们的临床症状、抗体水平、细胞因子水平、T 细胞增殖和调节性 T 细胞数量。

结果

在挑战前接受高剂量 Der f 舌下疫苗治疗的小鼠表现出气道高反应性、肺炎症和黏液产生等症状减轻,支气管肺泡灌洗液中的嗜酸性粒细胞也减少。有趣的是,高剂量 Der f 舌下疫苗组中诱导了 Der-f 特异性 IgE 反应减少和 Der-f 特异性 IgA 和 IgG1 反应增加。我们还观察到脾细胞和支气管肺泡灌洗液中白细胞介素-4 减少,干扰素-γ和白细胞介素-10 增加,抑制了脾 Der-f 特异性 T 细胞增殖,并增加了脾中的 CD4+CD25+Foxp3+调节性 T 细胞。然而,接受低剂量 Der f 舌下疫苗治疗的小鼠发展为过敏性哮喘。

结论

我们的结果表明,高剂量 Der f 舌下疫苗可能通过诱导调节性 T 细胞和 Th1 反应在小鼠变应性哮喘中发挥免疫保护作用。

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