IL-21/IL-21R介导的CD4^(+)T细胞在沙眼衣原体小鼠肺炎菌株呼吸道感染中的作用

Role of IL-21/IL-21R-mediated CD4^(+) T cells in Chlamydia muridarum respiratory infection

目的:探讨IL-21/IL-21R介导的CD4^(+)T细胞在沙眼衣原体呼吸道感染中的作用。方法:利用C57BL/6小鼠(WT小鼠)和IL-21R-/-小鼠,鼻腔吸入沙眼衣原体小鼠肺炎菌株(Chlamydia muridarum;Cm)建立小鼠沙眼衣原体呼吸道感染模型。流式细胞术检测小鼠Cm呼吸道感染后0、3、7、14 d小鼠肺、脾组织中CD4^(+)T细胞数量、活化程度和功能,ELISA分析脾细胞培养上清中IFN-γ和IL-4的含量。监测过继转移WT-CD4^(+)T细胞和IL-21R-/--CD4^(+)T细胞的na?ve WT小鼠Cm呼吸道感染后的体重变化,并分析感染后14 d的肺部细菌载量和病理情况,流式细胞术检测肺中性粒细胞(CD45+CD11b+Gr-1 high)、肺泡巨噬细胞(CD45+F4/80+CD11c high)、Th1(IFN-γ+CD4^(+))和Th2(IL-4^(+)CD4^(+))细胞的比例,ELISA分析脾细胞培养上清中IFN-γ和IL-4的含量。结果:Cm呼吸道感染后,与WT小鼠相比,IL-21R-/-小鼠脾、肺组织CD4^(+)T细胞数量和活化程度以及Th1细胞比例均升高,Th2细胞比例下降,脾细胞培养上清中IFN-γ含量升高,IL-4含量下降。过继转移IL-21R-/--CD4^(+)T细胞的受体小鼠在Cm呼吸道感染后体重下降幅度减小,肺组织细菌载量和病理情况减轻,肺Th1细胞比例升高,脾细胞培养上清中IFN-γ含量增加。结论:IL-21/IL-21R介导的CD4^(+)T细胞通过抑制Th1细胞免疫应答加重Cm呼吸道感染。

Objective To investigate the role of IL-21/IL-21R-mediated CD4^(+)T cells in Chlamydia muridarum(Cm)respiratory infection.Methods C57BL/6 mice(WT mice)and IL-21R-/-mice were used to establish the models of Cm respiratory infection through intranasal inhalation of Cm.Flow cytometry was used to detect the proportion,number,activity and function of CD4^(+)T cells in lung and spleen tissues at 0,3,7 and 14 d after Cm respiratory tract infection.IFN-γand IL-4 levels in spleen cell culture supernatants were detected by ELISA.Naïve WT mice were transferred with CD4^(+)T cells in the spleen tissues of IL-21R-/-mice or WT mice on 7 d after infection and given Cm intranasally 2 h later.Then the mice were weighed daily and sacrificed on 14 d after infection.The bacterial load and pathological changes in lung were analyzed.Flow cytometry was performed to detect the proportions and numbers of neutrophils(CD45+CD11b+Gr-1high)and alveolar macrophages(CD45+F4/80+CD11chigh)as well as the proportions of Th1(IFN-γ+CD4^(+))and Th2(IL-4^(+)CD4^(+))cells.ELISA was also performed to measure IFN-γand IL-4 levels in spleen cell culture supernatants.Results Compared with WT mice,IL-21R-/-mice showed elevated numbers and enhanced activation of CD4^(+)T cells,increased proportion of Th1 cells and decreased proportion of Th2 cells in spleen and lung tissues after Cm respiratory infection.Besides,IFN-γlevels increased,while IL-4 levels decreased in spleen cell culture supernatants of IL-21R-/-mice.After Cm infection,the naïve WT transferred with CD4^(+)T cells from IL-21R-/-mice showed less body weight loss,reduced bacterial load and alleviated pathological changes in lung tissues,increased proportion of Th1 cells in lung tissue and higher IFN-γlevel in spleen cell culture supernatants.Conclusions IL-21/IL-21R-mediated CD4^(+)T cells could aggravate Cm respiratory infection by suppressing Th1 cell immune responses.