CD4^+CD25^+调节性T细胞在过敏性哮喘和无症状的过敏者中表达的差异  

Different Responses of CD4^+CD25^+ Regulatory T Cells in Allergic Asthma Patients and Asymptomatic Sensitised People After Stimulation with Allergen in Vitro

作　　者：王丽慧[1] 杨炯[1] 杨亦斌[1] 

机构地区：[1]武汉大学中南医院呼吸内科,湖北武汉430071

出　　处：《武汉大学学报（医学版）》2011年第4期440-445,546,共7页Medical Journal of Wuhan University

摘　　要：目的:比较过敏性哮喘患者、无症状的过敏者和不过敏的健康人外周血CD4+CD25+调节性T细胞(Treg)数量的差异及对特异性过敏原刺激的反应。方法:选取急性发作期的尘螨过敏性哮喘患者20例,无症状的尘螨过敏者24例,不过敏的健康人22例,分离外周血单个核细胞(PBMC)并进行CFSE染色,分别在不刺激和1mg/L尘螨抗原(rDer p 1)刺激情况下体外培养7d,流式细胞仪检测CD4+CD25+Treg的比率和分裂指数;ELISA法检测各组细胞培养上清液和血清中白细胞介素-4(IL-4)和干扰素-γ(IFN-γ)的水平。结果:过敏性哮喘患者CD4+CD25+Treg比率和IFN-γ基础水平均低于无症状的尘螨过敏者和不过敏的健康人,且过敏原刺激后增加不明显;但IL-4的基础水平最高,过敏原刺激后差异更显著。无论刺激与否,无症状的尘螨过敏者CD4+CD25+Treg比率均与不过敏的健康人的水平接近。但过敏原刺激后无症状的尘螨过敏者CD4+CD25+Treg比率高于过敏性哮喘患者,且存在高水平的IFN-γ反应。结论:接触过敏原后,过敏性哮喘患者和无症状的过敏者表现出不同的免疫反应模式。过敏性哮喘患者抗原特异性CD4+CD25+Treg反应不足,存在过高Th2反应。无症状过敏的发生可能与机体对特异性过敏原刺激产生高水平的CD4+CD25+Treg反应及高水平的IFN-γ反应有关。Objective：To determine whether there are differences in the numbers and the responses of CD4＋CD25＋ regulatory T cells（Treg） in allergic asthmatics and people asymtomatic sensitised to specific allergen after specific allergen exposure.Methods：Peripheral blood mononuclear cells（PBMCs） were isolated from 20 patients sensitized to house dust mite with asthma,24 asymptomatic subjects sensitized to house dust mite,and 22 non-allergic subjects.Cells were cultured without stimulation and with 1 mg/L antigen of dust mite rDer p 1.Frequencies and division index of CD4＋CD25＋ Tregs were measured by flow cytometry and analyzed by CFSE diluent analysis.Concentrations of IL-4 and IFN-γ in culture supernatants and serums were determined by ELISA.Results：①PBMCs derived from sensitized asthmatic patients had the lowest baseline level of CD4＋CD25＋ Tregs and IFN-γ,and the levels did not increased much after allergen stimulating.Sensitized asthmatic patients also had the highest level of IL-4 both in un-stimulated and rDer p 1-stimulated cultures.②Percentages of CD4＋CD25＋ Tregs in sensitized asymptomatic group were similar to those in non-allergic group both in un-stimulated and rDer p 1-stimulated cultures.PBMCs derived from sensitized asymptomatic subjects had higher percentages of CD4＋CD25＋ Tregs than those from sensitized asthmatic patients in rDer p 1-stimulated cultures,and had the highest levels of IFN-γ responses to allergen among the three groups.Conclusion：Patients with allergic asthma had insufficient CD4＋CD25＋ Treg cell responses and excessive Th2 responses to specific allergens.The high levels of Treg responses and IFN-γ responses to specific allergen can partly explain the immunological characteristics associated with sensitized asymptomatics.

关 键 词：哮喘 调节性T细胞 过敏原 干扰素-γ 白细胞介素-4 

分 类 号：R562.25[医药卫生—呼吸系统]