Asthma is induced by intranasal coadministration of allergen and natural killer T-cell ligand in a mouse model
Asthma is induced by intranasal coadministration of allergen and natural killer T-cell ligand in a mouse model
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DOI：
10.1016/j.jaci.2004.09.004
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发表时间：
2004-12-01
影响因子：
14.2
通讯作者：
Kang, CY
中科院分区：
文献类型：
--
作者：
Kim, JO;Kim, DH;Kang, CY
背景：过敏性哮喘是由T(H)2驱动的免疫反应引起的一种炎症性肺部疾病。目的：探讨CD1d诱导的自然杀伤T细胞(NKT)细胞在T(H)2依赖的过敏性哮喘小鼠模型中的作用。方法：采用NKT细胞配体α-半乳糖神经酰胺(AlphaGC)，观察NKT细胞在哮喘发病中的作用。我们用不同的抗原和αGC组合鼻腔致敏Balb/c小鼠，连续3天，并在2周后用卵清蛋白气雾剂攻击它们。结果：仅卵白蛋白+αGC联合免疫时，Balb/c小鼠出现气道高反应性、嗜酸性粒细胞增多、IgE水平升高和T(H)2细胞因子的产生。单独的卵白蛋白、单独的α-GC或BSA+α-GC免疫的小鼠不会诱发哮喘。对NKT细胞缺陷或CD4(+)T细胞缺陷小鼠经鼻腔暴露于卵白蛋白加αGC的研究没有显示哮喘的发生。结论：NKT细胞在哮喘变应原致敏和病理状态中起重要作用。此外，我们使用α-GC建立的新的哮喘模型将非常有用地诱导哮喘，并剖析NKT细胞和其他细胞在哮喘中的作用。
Background: Allergic asthma is an inflammatory lung disease caused by a T(H)2-driven immune response. However, intranasal exposures to soluble antigen lead to mucosal tolerance, and the mechanism involved in generation of T(H)2 responses to inert inhaled allergens is unknown.Objective: The aim of this study was to investigate whether CD1d-restrieted natural killer T (NKT) cells can contribute to the induction of T(H)2-dependent allergic asthma in a mouse model.Methods: To investigate the effect of NKT cells on the development of asthma, NKT cell ligand, alpha-galactosylceramide (alphaGC), was used with antigens. We intranasally sensitized Balb/c mice with various combinations of antigen and alphaGC for 3 consecutive days and challenged them 2 weeks later with an aerosol of ovalbumin. NKT cell-deficient or To cell-deficient mice were immunized by administering ovalbumin and alphaGC together, and ovalbumin inhalation.Results: Only when immunized with ovalbumin plus alphaGC, airway hyperreactivity, airway eosinophils, elevated IgE level, and T(H)2-cytokine production were observed in Balb/c mice. Ovalbumin alone, alphaGC alone, or BSA plus alphaGC-immunized mice did not induce asthma. Studies in NKT cell-deficient, or CD4(+) T-cell-deficient mice intranasally exposed to ovalbumin plus alphaGC did not show the development of asthma. An increase of NKT cells in bronchoalveolar lavage was observed in the pathologic states.Conclusion: These data demonstrate that NKT cells can play crucial roles in allergen sensitization and pathologic states in asthma. Furthermore, our new asthma model using alphaGC will be very useful to induce asthma and to dissect the role of NKT cells and other cells in asthma.