哮喘患者急性加重期滤泡辅助型T细胞的分化水平及临床意义

The differentiation and clinical significance of follicular helper T cells during acute exacerbation in asthma patients

目的观察滤泡辅助型T细胞(Tfh细胞)在支气管哮喘患者急性发作期和治疗后的分化水平,探讨Tfh细胞是否在哮喘中存在分化异常及其临床意义。方法采用流式细胞术检测健康志愿者、哮喘患者急性发作期及治疗后外周血单个核细胞中CD4~^+CXCR5~^+T细胞、CD4~^+ICOS^+T细胞、CD4~^+CXCR5~^+ICOS~^+T细胞的比例;反转录PCR法检测CD4^+T细胞中Bcl-6mRNA的水平;ELISA检测血浆白细胞介素21(IL-21)的水平;采用直线回归统计学分析IL-21与患者第一秒用力呼气容积/用力肺活量百分比(FEV1/FVC)及第一秒用力呼气容积/预计值百分比(FEV1/Pre)之间的相关性。结果哮喘患者CD4~^+CXCR5~^+细胞、CD4~^+CXCR5~^+ICOS~^+T细胞比例、Bcl-6 mRNA表达水平、IL-21水平均显著高于正常对照组;治疗后哮喘患者CD4~^+CXCR5~^+细胞、CD4~^+ICOS~^+细胞、CD4~^+CXCR5~^+ICOS~^+T细胞表达比例、Bcl-6 mRNA表达水平、IL-21水平均显著低于急性发作时;哮喘患者IL-21表达水平与患者FEV1/FVC、FEV1/Pre存在负相关。结论 Tfh细胞在哮喘急性期存在分化增强,治疗后Tfh细胞分化减弱,提示Tfh细胞可能参与哮喘的炎症反应,其水平可能反映哮喘患者气道受限程度。

Objective To observe the differentiation of follicular helper T （Tfh） cells in asthma patients during acute exacerbation and post-treatment periods, and explore the clinical significance of Tfh cells in asthma. Methods We detected the percentages of CD4＋ CXCR5 ＋, CD4 ＋ ICOS＋, CD4 ＋ CXCR5 ＋ ICOS＋ T cells in peripheral blood mononuclear cells （PBMCs） by flow cytometry, the level of Bcl-6 mRNA in CD4＋ T cells by reverse transcription PCR, and the level of interleukin 21 （IL-21） in plasma by ELISA in healthy controls and asthma patients during acute exacerbation and post-treatment release periods. The linear regression analysis was used to analyze the correlations of the level of IL-21 in plasma with forced expiratory volume in one second/forced vital capacity （FEV]/FVC） and forced expiratory volume in one second/prediction （FEVI/Pre） in acute exacerbation period of asthma patients. Results The percentages of CD4 ＋ CXCFL5 ＋, CD4 ＋ CXCR5 ＋ ICOS ＋ T cells in PBMCs, the level of Bcl-6 mRNA in CD4＋T cells, and the level of IL-21 in plasma increased in acute exacerbation of the asthma patients compared to the healthy controls. After treatment, the percentages of CD4 ＋ CXCR5 ＋ , CD4 ＋ ICOS ~ , CD4 ＋ CXCFLS＋ ICOS＋ T cells in PBMCs, the level of Bcl-6 mRNA in CD4＋T cells, and the level of IL-21 in plasma in asthma patients were all reduced as compared with the acute exacerbation period. There were negative correlations between IL-21 and lung function parameters such as FEV1/FVC and FEV1/Pre. Condusien The differentiation of Tfh cells was enhanced in acute exacerbation of asthma patients, and ameliorated after treatment. Tfh cells may participate in the inflammatory reaction of asthma, and the differentiation degree of Tfh cells may reflect the extent of airway limitation in asthma patients.