双阴性T细胞介导了过敏性哮喘的lag3依赖抗原特异性保护
2019/10/17
摘要
过敏性哮喘是一种气道炎症性疾病，没有令人满意的传统治疗方法能够控制其潜在的病理。因此，能够克服免疫失调的有害影响的新方法是可取的。我们采用卵清蛋白(OVA)肽引物CD4CD8双阴性T细胞静脉输注OVA致变应性哮喘小鼠模型，发现OVA诱导的气道高反应性、肺炎症、黏液生成和OVA特异性IgG/IgE生成均受到明显抑制。ova特异性DNT细胞的免疫抑制功能依赖于抑制CD11b树突状细胞功能、T滤泡辅助细胞增殖和IL-21的产生。机制上，Lag3有助于MHC-II抗原的识别和滋养细胞作用，从而通过DNT细胞调节抗原特异性免疫调节。体外产生的特异性过敏原DNT细胞在缓解气道炎症方面的有效性，因此支持了DNT细胞治疗过敏性哮喘的潜在应用。
Abstract
Allergic asthma is an inflammatory disorder of the airway without satisfactory traditional therapies capable of controlling the underlying pathology. New approaches that can overcome the detrimental effects of immune dysregulation are thus desirable. Here we adoptively transfer ovalbumin (OVA) peptide-primed CD4CD8 double negative T (DNT) cells intravenously into a mouse model of OVA-induced allergic asthma to find that OVA-induced airway hyperresponsiveness, lung inflammation, mucus production and OVA-specific IgG/IgE production are significantly suppressed. The immunosuppressive function of the OVA-specific DNT cells is dependent on the inhibition of CD11b dendritic cell function, T follicular helper cell proliferation, and IL-21 production. Mechanistically, Lag3 contributes to MHC-II antigen recognition and trogocytosis, thereby modulating the antigen-specific immune regulation by DNT cells. The effectiveness of ex vivo-generated allergen-specific DNT cells in alleviating airway inflammation thus supports the potential utilization of DNT cell-based therapy for the treatment of allergic asthma.
过敏性哮喘是一种气道炎症性疾病，没有令人满意的传统治疗方法能够控制其潜在的病理。因此，能够克服免疫失调的有害影响的新方法是可取的。我们采用卵清蛋白(OVA)肽引物CD4CD8双阴性T细胞静脉输注OVA致变应性哮喘小鼠模型，发现OVA诱导的气道高反应性、肺炎症、黏液生成和OVA特异性IgG/IgE生成均受到明显抑制。ova特异性DNT细胞的免疫抑制功能依赖于抑制CD11b树突状细胞功能、T滤泡辅助细胞增殖和IL-21的产生。机制上，Lag3有助于MHC-II抗原的识别和滋养细胞作用，从而通过DNT细胞调节抗原特异性免疫调节。体外产生的特异性过敏原DNT细胞在缓解气道炎症方面的有效性，因此支持了DNT细胞治疗过敏性哮喘的潜在应用。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Nat Commun. 2019 Sep 18;10(1):4246. doi: 10.1038/s41467-019-12243-0)
(Nat Commun. 2019 Sep 18;10(1):4246. doi: 10.1038/s41467-019-12243-0)
Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma.
Tian D, Yang L, Wang S, Zhu Y, Shi W, Zhang C, Jin H, Tian Y, Xu H, Sun G, Liu K, Zhang Z, Zhang D.Abstract
Allergic asthma is an inflammatory disorder of the airway without satisfactory traditional therapies capable of controlling the underlying pathology. New approaches that can overcome the detrimental effects of immune dysregulation are thus desirable. Here we adoptively transfer ovalbumin (OVA) peptide-primed CD4CD8 double negative T (DNT) cells intravenously into a mouse model of OVA-induced allergic asthma to find that OVA-induced airway hyperresponsiveness, lung inflammation, mucus production and OVA-specific IgG/IgE production are significantly suppressed. The immunosuppressive function of the OVA-specific DNT cells is dependent on the inhibition of CD11b dendritic cell function, T follicular helper cell proliferation, and IL-21 production. Mechanistically, Lag3 contributes to MHC-II antigen recognition and trogocytosis, thereby modulating the antigen-specific immune regulation by DNT cells. The effectiveness of ex vivo-generated allergen-specific DNT cells in alleviating airway inflammation thus supports the potential utilization of DNT cell-based therapy for the treatment of allergic asthma.
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