Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma
Double negative T cells mediate Lag3-dependent antigen-specific protection in allergic asthma
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双阴性 T 细胞介导过敏性哮喘中 Lag3 依赖性抗原特异性保护
DOI：
10.1038/s41467-019-12243-0
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发表时间：
2019-09-18
影响因子：
16.6
通讯作者：
Zhang, Dong
中科院分区：
文献类型：
--
作者：
Tian, Dan;Yang, Lu;Zhang, Dong
过敏性哮喘是一种气道炎症性疾病，传统疗法无法控制其潜在的病理变化。因此，需要能够克服免疫失调的有害影响的新方法。在这里，我们将卵清蛋白（OVA）肽致敏的CD 4 − CD 8 −双阴性T（DNT）细胞静脉内转移到OVA诱导的过敏性哮喘小鼠模型中，发现OVA诱导的气道高反应性，肺部炎症，粘液产生和OVA特异性IgG/IgE产生被显着抑制。OVA特异性DNT细胞的免疫抑制功能依赖于对CD 11b+树突状细胞功能、T滤泡辅助细胞增殖和IL-21产生的抑制。在机制上，Lag 3有助于MHC-II抗原识别和胞刺，从而调节DNT细胞的抗原特异性免疫调节。因此，体外产生的过敏原特异性DNT细胞在减轻气道炎症中的有效性支持了基于DNT细胞的疗法用于治疗过敏性哮喘的潜在用途。
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 CD4−CD8−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.