Kim Jae-Ouk, Kim Dong-Hyeon, Chang Woo-Sung, Hong Changwan, Park Se-Ho, Kim Sanghee, Kang Chang-Yuil
Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Korea.
J Allergy Clin Immunol. 2004 Dec;114(6):1332-8. doi: 10.1016/j.jaci.2004.09.004.
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.
The aim of this study was to investigate whether CD1d-restricted natural killer T (NKT) cells can contribute to the induction of T(H)2-dependent allergic asthma in a mouse model.
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 T(H) cell-deficient mice were immunized by administering ovalbumin and alphaGC together, and ovalbumin inhalation.
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.
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.
过敏性哮喘是一种由辅助性T细胞2（TH2）驱动的免疫反应所引起的炎症性肺部疾病。然而，经鼻暴露于可溶性抗原会导致黏膜耐受，且对惰性吸入性过敏原产生TH2反应的相关机制尚不清楚。
本研究旨在探讨CD1d限制性自然杀伤T（NKT）细胞是否能在小鼠模型中促进TH2依赖性过敏性哮喘的诱导。
为研究NKT细胞对哮喘发展的影响，将NKT细胞配体α-半乳糖神经酰胺（αGC）与抗原一起使用。我们用抗原和αGC的不同组合对Balb/c小鼠进行连续3天的经鼻致敏，并在2周后用卵清蛋白气雾剂对其进行激发。通过同时给予卵清蛋白和αGC以及卵清蛋白吸入对NKT细胞缺陷或TH细胞缺陷小鼠进行免疫。
仅在使用卵清蛋白加αGC免疫时，Balb/c小鼠中观察到气道高反应性、气道嗜酸性粒细胞、IgE水平升高以及TH2细胞因子产生。单独使用卵清蛋白、单独使用αGC或牛血清白蛋白加αGC免疫的小鼠未诱发哮喘。对经鼻暴露于卵清蛋白加αGC的NKT细胞缺陷或CD4+T细胞缺陷小鼠的研究未显示哮喘的发展。在病理状态下观察到支气管肺泡灌洗中NKT细胞增加。
这些数据表明，NKT细胞在哮喘的过敏原致敏和病理状态中可发挥关键作用。此外，我们使用αGC的新哮喘模型对于诱导哮喘以及剖析NKT细胞和其他细胞在哮喘中的作用将非常有用。
