Liu Zhigang, Guo Hua, Wu Yiaojiong, Yu Haiqiong, Yang Haitao, Li Jing
Allergy and Immunology Institute, School of Medicine, Shenzhen University, Shenzhen, PR China.
Int Arch Allergy Immunol. 2009;150(3):221-8. doi: 10.1159/000222674. Epub 2009 Jun 3.
Local nasal immunotherapy has been reported to be effective for airway allergic diseases. A biodegradable material, chitosan (CS), has been reported to be safe and effective in allergen delivery. In this study, we tested immunotherapeutic efficiency by intranasal administration of Der f entrapped in CS microparticles to sensitized mice.
BALB/c mice were sensitized intraperitoneally with Der f extract absorbed to alum, followed by intranasal treatment with PBS, CS, Der f or Der f-CS nano-vaccine for 6 weeks. The mice were subsequently challenged intranasally with Der f extract for 1 week, and we analyzed their clinical symptoms, antibody expression levels, cytokine levels, T cell proliferation and regulatory T cell numbers.
Mice treated with intranasal Der f-CS nano-vaccine prior to challenge displayed an alleviated spectrum of symptoms including airway hyper-reactivity, lung inflammation and mucus production and had fewer eosinophilic cells in bronchoalveolar lavage fluid (BALF). Interestingly, the cytokine levels in Der f-specific IgE were reduced, but IgA in serum and BALF was increased. We also observed that IL-4 was reduced and IFN-gamma and IL-10 were increased among splenocytes and in BALF, which inhibits Der f-specific T-cell proliferation in splenocytes and increases regulatory T cells in the spleen. However, the mice challenged without intranasal Der f or Der f-CS vaccine treatment developed allergic asthma.
Our results illustrate that intranasal administration of Der f-CS nano-vaccine plays roles in immunologic protection in murine allergic asthma by inducing regulatory T cells and Th1-type reaction.
局部鼻内免疫疗法已被报道对气道过敏性疾病有效。一种可生物降解的材料,壳聚糖(CS),已被报道在变应原递送中安全有效。在本研究中,我们通过向致敏小鼠鼻内给予包裹在CS微粒中的Der f来测试免疫治疗效果。
用吸附于明矾的Der f提取物对BALB/c小鼠进行腹腔致敏,随后用PBS、CS、Der f或Der f-CS纳米疫苗进行鼻内治疗6周。随后,用Der f提取物对小鼠进行鼻内激发1周,我们分析了它们的临床症状、抗体表达水平、细胞因子水平、T细胞增殖和调节性T细胞数量。
在激发前接受鼻内Der f-CS纳米疫苗治疗的小鼠表现出一系列症状减轻,包括气道高反应性、肺部炎症和黏液产生,支气管肺泡灌洗液(BALF)中的嗜酸性粒细胞较少。有趣的是,Der f特异性IgE中的细胞因子水平降低,但血清和BALF中的IgA增加。我们还观察到,脾细胞和BALF中的IL-4降低,IFN-γ和IL-10增加,这抑制了脾细胞中Der f特异性T细胞的增殖,并增加了脾脏中的调节性T细胞。然而,未接受鼻内Der f或Der f-CS疫苗治疗而被激发的小鼠发生了过敏性哮喘。
我们的结果表明,鼻内给予Der f-CS纳米疫苗通过诱导调节性T细胞和Th1型反应在小鼠过敏性哮喘的免疫保护中发挥作用。