天然调节T细胞与结核病免疫病理关联  

Regulatory T cells are increased in tuberculosis patients and closely correlate with its immunopathology

作　　者：赵雁林 王敬[2] 张海青[3] 易玲[4] 李惠文[4] 韦攀健[4] 赵丹[3] 王小珏[4] 郑小芳[4] 张洪涛[4] 

机构地区：[1]结核病国家参比实验室,北京101149 [2]北京市结核病胸部肿瘤研究所结核内科,101149 [3]北京市结核病胸部肿瘤研究所病理科,101149 [4]北京市结核病胸部肿瘤研究所中心实验室,101149

出　　处：《中华微生物学和免疫学杂志》2010年第5期460-465,共6页Chinese Journal of Microbiology and Immunology

摘　　要：目的 检测调节性T细胞（Tr）在结核病病人是否增高,确证Tr与结核免疫病理的关联性,为Tr功能研究提供疾病模型.方法 流式细胞术（FACS）分选CD3＋CD4＋T及CD3＋CD8＋T等主要淋巴细胞亚群,通过RT-PCR测定Foxp3基因在正常和结核病病人T细胞亚群中的表达,FACS多色分析Foxp3 T细胞在CD4＋CD25＋细胞群体中的分布,累积病例分析Tr细胞在外周血扩增情况,免疫组化方法分析Tr在结核病理的浸润,结合临床资料分析Tr数量的改变与结核病的关联性.结果 Foxp3基因在正常和结核病病人CD3＋ CD4＋T细胞中特异性扩增,FACS分析表明foxp3主要表达于CD4＋ CD25high亚群中,占CD4＋ CD25highT细胞的80%以上,以CD4＋CD2high Foxp3＋三联标志检测40例正常与51例活动性结核病病人外周血Tr占CD4＋T细胞比例分别为（0.23±0.20）%和（1.01±1.00）%,结核病病人较正常人高4.4倍,Tr在结核病明显扩增（P〈0.01）,结核病理组织中有高频率Foxp3＋细胞浸润.Tr扩增与结核病有效治疗和预后的关联性有深入探讨价值.结论 Tr细胞在结核病病人增高,并与结核免疫病理损伤相关,结核病可作为Tr细胞功能研究的疾病模型.Objective To determine whether regulatory T cells（Tr）are increased in patients with tuberculosis and whether they are associated with its immunopathology.Meantime,to investigate the possibility of tuberculosis（TB）as a model for studying Tr functions.Methods The lymphocyte subsets were isolated from peripheral blood mononuclear cells by sorting with flow cytometry.Total cellular RNA was extracted and RT-PCR was performed to detect the Foxp3 mRNA in purified CD3＋CIM＋T cells,CD3＋CD8＋T cells and non-CD3＋CD4＋CD8＋T cells.Using FACS analysis.we further investigated the distribution of Foxp3＋ population in CD4＋ CD25＋T cells.Finally,we compared the percentage of CD4＋CD25highFoxp3＋T cells present in 51 active patients with tuberculosis and 40 uninfected healthy control subjects by FACS.The detection of Tr infiltration of Foxp3＋ cells were performed with immunohistochemistry（IHC）method on tuberculosis pathological sections.Results Foxp3 was specific expressed in CD3＋CD4＋T cells,either in tuberculosis patients or healthy control subjects.Foxp3＋ T cells took about 85%fraction of CD4＋ CD25highpopulation.We used CD4＋CD25high Foxp3＋as a detective markers for Tr in the FACS analysis.The results showed that patients with active TB had a 4.4 fold higher percentage within the CD4＋T cells in peripheral blood compared to healthy control group（modian,1.01%vs 0.23%,P〈0.01）.Much higher frequency of Tr were found along with T cells infiltration at the tuberculosis pathological tissues.A few individuals that we can followed indicated the expanded Tr was declined after curative treatment with operation.Conclusion Tr cells are increased in tuberculosis patients and closely correlate with its immunopathology.Tuberculosis should be a valuable model for Tr functional study.

关 键 词：天然调节性T细胞 CD4+CD25highFoxp3+ 结核病 免疫病理 

分 类 号：R52[医药卫生—内科学]