Li Ping, Li Ze, Zhang Guqin, Yang Jiong, Chen Junwen
Department of Respiratory and Critical Care Medicine, Affiliated Xiangyang Hospital of Hubei University of Medicine, Xiangyang, China.
Department of Respiratory and Critical Care Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Iran J Allergy Asthma Immunol. 2019 Aug 17;18(4):369-378. doi: 10.18502/ijaai.v18i4.1415.
Interleukin (IL)-4-producing-CD8 (cytotoxic T cells, Tc) contribute to lung eosinophilia and airway hyper-responsiveness (AHR) to an antigen. CD4+CD25+ regulatory T cells (Tregs) attenuate airway inflammation and AHR. This study investigated whether Tregs decrease Tc2frequencies in ovalbumin (OVA)-induced asthma model of mice. Female C57BL/6 mice were sensitized with OVA intraperitoneally and challenged with OVA intranasally to induce allergic asthma model. Tregs were sorted by fluorescence activated cell sorting (FACS) and magnetic activated cell sorting (MACS) microbeads. OVA-sensitized mice were injected with Tregs or phosphate buffer saline (PBS) by tail vein ahead of the first challenge. Airway inflammation and airway hyper-responsiveness (AHR)were evaluated by histological analysis and invasive method, respectively. OVA-specific IgE and cytokine levels were detected by ELISA. Flow cytometry was used to detect the percentages of Tc1 and Tc2. Gata3 and T-bet mRNA was determined by quantitative PCR (qPCR). OVA-sensitized and challenged mice displayed typical asthma features, which included eosinophilic airway inflammation, higher levels of Th2 cytokines and AHR. Gata3 mRNA, Tc2 frequencies and OVA-specific IgE levels were significantly increased in OVA-sensitized and challenged mice. Compared to PBS treatment, Tregs decreased Tc2 frequencies, airway inflammation, Th2 cytokine levels and AHR in OVA-sensitized and challenged mice. IL-13 levels were negatively correlated with Tc1 frequencies and with IFNg levels in experimental mice. Our results demonstrated that Tregs could prevent airway inflammation and AHR by decreasing Tc2 frequencies and cytokine levels in OVA-induced asthma model of mice, supporting Tregmight be as a potent therapeutic target for alleviating airway inflammation and AHR.
产生白细胞介素（IL）-4的CD8（细胞毒性T细胞，Tc）会导致肺部嗜酸性粒细胞增多以及对抗原的气道高反应性（AHR）。CD4+CD25+调节性T细胞（Tregs）可减轻气道炎症和AHR。本研究调查了在卵清蛋白（OVA）诱导的小鼠哮喘模型中，Tregs是否会降低Tc2细胞频率。雌性C57BL/6小鼠经腹腔注射OVA致敏，并经鼻内给予OVA激发以诱导过敏性哮喘模型。通过荧光激活细胞分选（FACS）和磁激活细胞分选（MACS）微珠对Tregs进行分选。在首次激发前，经尾静脉向OVA致敏小鼠注射Tregs或磷酸盐缓冲盐水（PBS）。分别通过组织学分析和侵入性方法评估气道炎症和气道高反应性（AHR）。通过酶联免疫吸附测定（ELISA）检测OVA特异性IgE和细胞因子水平。采用流式细胞术检测Tc1和Tc2的百分比。通过定量聚合酶链反应（qPCR）测定Gata3和T-bet mRNA。经OVA致敏和激发的小鼠表现出典型的哮喘特征，包括嗜酸性气道炎症、较高水平的Th2细胞因子和AHR。在经OVA致敏和激发的小鼠中，Gata3 mRNA、Tc2细胞频率和OVA特异性IgE水平显著升高。与PBS处理相比，Tregs降低了经OVA致敏和激发小鼠的Tc2细胞频率、气道炎症、Th2细胞因子水平和AHR。在实验小鼠中，IL-13水平与Tc1细胞频率以及IFNγ水平呈负相关。我们的结果表明，在OVA诱导的小鼠哮喘模型中，Tregs可通过降低Tc2细胞频率和细胞因子水平来预防气道炎症和AHR，支持Tregs可能作为减轻气道炎症和AHR的有效治疗靶点。
