IL-15 prevents allergic rhinitis through reactivation of antigen-specific CD8+ cells
IL-15 prevents allergic rhinitis through reactivation of antigen-specific CD8+ cells
复制标题
DOI：
10.1016/j.jaci.2006.02.018
复制
发表时间：
2006-06-01
影响因子：
14.2
通讯作者：
Yoshikai, Yasunobu
中科院分区：
文献类型：
--
作者：
Aoi, Noriaki;Masuda, Tokuko;Yoshikai, Yasunobu
背景资料：变应性鼻炎是最常见的变应性炎症性疾病之一，其特征在于具有抗原特异性IgE合成的占优势的T（H）2反应。IL-15在激活和维持能够产生IFN-γ的记忆性CD 8（+）T细胞中起重要作用，IFN-γ调节TH 2应答。目的：为了研究内源性IL-15在变应性炎症中的作用，我们检测了用卵白蛋白致敏的IL-15敲除（KO）小鼠，然后用卵白蛋白鼻内再激发的变应性鼻炎。IL-15 KO小鼠在第0天用卵清蛋白/完全弗氏佐剂腹腔内致敏，在第7天用卵清蛋白/1FA腹腔内致敏，然后在第21、22、23、24和25天用卵清蛋白鼻内攻击。检查鼻部症状和组织学变化。通过ELISA测量IgE产生和T（H）2应答。结果：IL-15 KO小鼠的IgE产生水平和TH 2应答水平与对照小鼠相当。然而，打喷嚏，嗜酸性粒细胞浸润到鼻粘膜，和TH 2细胞因子的生产加剧卵白蛋白致敏的IL-15 KO小鼠鼻内攻击后，卵白蛋白。从卵清蛋白致敏的小鼠中连续转移CD 8（+）T细胞抑制了小鼠的T（H）2反应，但在IL-15 KO小鼠中没有。IL-15与卵清蛋白的管理显着防止过敏性鼻炎在卵清蛋白致敏mice.Conclusion的发展：我们证明与IL-15 KO小鼠，内源性IL-15在抑制过敏性鼻炎在效应阶段起着重要作用。鼻内注射IL-15是一种有效的治疗方法，以控制变应性鼻炎。临床意义：鼻内注射重组IL-15可能成为新的免疫治疗变应性鼻炎。
Background: Allergic rhinitis is one of the most common allergic inflammatory diseases characterized by a predominant T(H)2 response with antigen-specific IgE synthesis. IL-15 plays important roles in activation and maintenance of memory CD8(+)T cells capable of producing IFN-gamma, which regulates TH2 responses.Objective: To investigate the roles of endogenous IL-15 in allergic inflammation, we examined allergic rhinitis in IL-15 knockout (KO) mice sensitized with ovalbumin followed by intranasal rechallenge with ovalbumin.Methods: IL-15KO mice were sensitized intraperitoneaily with oval bumin/complete Freund's adjuvant on day 0 and ovalbumin/1FA on day 7, and then were intranasally challenged with ovalbumin on days 21, 22, 23, 24, and 25. Nasal symptoms and histologic changes were examined. IgE production and T(H)2 responses were measured by ELISA. Purified CD8+T cells or recombinant IL-15 were administered into ovalbumin-sensitized mice.Results: The levels of IgE production and TH2 responses in IL-15KO mice were comparable to those in control mice a er ovalbumin sensitization. However, sneezing, infiltration of eosinophils into the nasal mucosa, and TH2 cytokine production were aggravated in ovalbumin-sensitized IL-15KO mice after intranasal challenge with ovalbumin. Adoptive transfer of CD8(+) T cells from ovalbumin-sensitized mice suppressed the T(H)2 responses in mice but not in IL-15KO mice. Administration of IL-15 with oval bumin significantly prevented the development of allergic rhinitis in ovalbumin-sensitized mice.Conclusion: We demonstrate with IL-15KO mice that endogenous IL-15 plays an important role in suppression of allergic rhinitis at effector phase. Intranasal administration of IL-15 is useful as a therapeutic approach to control allergic rhinitis.Clinical implications: Intranasal administration of recombinant IL-15 might become new immunotherapy for allergic rhinitis.