重症肌无力患儿外周血滤泡调节性T细胞与滤泡辅助性T细胞变化及影响因素  

Changes of circulating Tfr and Tfh cells in children with myasthenia gravis

作　　者：崔亚杰[1] 陈芳[1] 郭燕军[1] 宋春兰[1] 

机构地区：[1]郑州市儿童医院重症监护室,450003

出　　处：《中华微生物学和免疫学杂志》2016年第10期746-752,共7页Chinese Journal of Microbiology and Immunology

基　　金：郑州市儿童医院重点专科基金

摘　　要：目的：观察重症肌无力（ MG）患儿外周血滤泡调节性T细胞（ Tfr细胞）和滤泡辅助性T细胞（ Tfh细胞）比值变化以及其影响因素。方法 MG患儿治疗前28例、治疗后15例和对照组20例,流式细胞术检测外周血CD4＋CXCR5＋ICOS＋Tfh细胞和CD4＋Foxp3＋CXCR5＋ ICOS＋Tfr细胞阳性表达；实时荧光定量 PCR检测转录因子及调控因子Bcl-6、c-MAF、Blimp-1和 PD-1 mRNA表达变化；ELISA检测血浆IL-2、IL-6、IL-10、IL-21和 Ach-Rab、PsMab 浓度水平,统计各组指标的差异。结果（1）与对照组相比,MG治疗前患儿外周血Tfh细胞数量增多,Tfr细胞数量减少,Tfr/Tfh细胞比值失衡；（2）CD4＋T细胞Bcl-6 mRNA及c-MAF mRNA较对照组明显增高,转录抑制因子Blimp-1 mRNA低于对照组；Treg细胞PD-1 mRNA明显低于对照组；（3）血浆细胞因子IL-2浓度降低,IL-21浓度增高。结论（1）外周血Tfr细胞数量减少,Tfh细胞数量增加,Tfr/Tfh细胞比值失衡可能参与了儿童重症肌无力的发病；（2）CD4＋T细胞Bcl-6、c-MAF mRNA 和Treg细胞 PD-1 mRNA过表达,Blimp-1 mRNA表达不足,以及局部微环境IL-2、IL-21浓度改变可能为造成Tfr/Tfh细胞分化失衡因素之一。Objective To investigate the changes of follicular regulatory T cells （ Tfr cells） and follicular T helper cells （ Tfh cells） in peripheral blood of children with myasthenia gravis （ MG） . Methods We recruited 28 MG patients and 20 healthy subjects in this study. The percentages of Tfh and Tfr cells in peripheral blood samples were measured by flow cytometry. Real-time PCR was performed to detect the ex-pression of transcription factors and regulatory factors of Bcl-6, c-MAF, Blimp-1 and PD-1 at mRNA level. ELISA was used to detect the levels of IL-2, IL-6, IL-10 and IL-21 in plasma samples and the titers of Ach-Rab and PsMab. Results Compared with the healthy subjects, the MG patients showed higher percentages of Tfh cells and lower percentages of Tfr cells before receiving treatment. The expression of Bcl-6 and c-MAF on CD4＋T lymphocytes cells at transcriptional level were significantly enhanced, while the expression of Blimp-1 on CD4＋T cells and the expression of PD-1 on Treg cells at transcriptional level were inhibited in the MG patients in comparison with those in healthy subjects. Moreover, decreased levels of IL-2 and increased levels of IL-21 were found in plasma samples collected from the MG patients. Conclusion The decreased percentages of Tfr cells and increased percentages of Tfh cells in patients with MG resulted in abnormal ratios of Tfr/Tfh cells, which might be involved in the immunological pathogenesis of MG. Several changes in the patients with MG might be responsible for the imbalanced ratio of Tfr/Tfh cells, which included changes of IL-2 and IL-21 in microenvironment, enhanced expression of Bcl-6 and c-MAF at mRNA level and inhibited expression of Blimp-1 at mRNA level on CD4＋T cells as well as over-expression of PD-1 at mRNA level on Treg cells.

关 键 词：重症肌无力 滤泡辅助性T细胞 滤泡调节性T细胞 

分 类 号：R746.1[医药卫生—神经病学与精神病学]