[儿童免疫性血小板减少症中循环滤泡调节性T细胞和滤泡辅助性T细胞的变化]
[The changes of circulating follicular regulatory T cells and follicular T helper cells in children immune thrombocytopenia].
作者信息
Cui Yajie, Guan Yujie, Liu Wei, Li Yan'ge, Li Huixia, Guo Mingfa
机构信息
Department of Hematology, Zhengzhou Children's Hospital, zhengzhou 450003, China.
出版信息
Zhonghua Xue Ye Xue Za Zhi. 2014 Nov;35(11):980-4. doi: 10.3760/cma.j.issn.0253-2727.2014.11.006.
OBJECTIVE
To investigate the changes and roles of follicular regulatory T cells (Tfr) and follicular T helper cells (Tfh) in the pathogenesis of children immune thrombocytopenia (ITP).
METHODS
32 untreated ITP patients, as well as 20 healthy controls were enrolled in this study. The proportion of circulating Tfr and Tfh cells were determined by flow cytometry; real-time PCR was performed to detect the expression of transcription factors and regulatory factors of Bcl-6, c-Maf, Blimp-1 and PD-1 mRNA; ELISA was used to detect plasma concentration of IL-2, IL-6, IL-10 and IL-21.
RESULTS
(1)The proportion of Tfh cells were significantly higher (P<0.05), while the Tfr cells and the ratio of tfr/Tfh cells in ITP patients were significantly lower than that in health controls (P<0.05); (2)Correlation analysis showed that the Tfr cells and the ratio of Tfr/Tfh were positively correlated with the platelet counts and negatively with the levels of PA-IgG, while the proportion of Tfh cells was positively correlated with the levels of PA-IgG and negatively with the platelet counts in peripheral blood; (3)Transcription levels of Bcl-6 and c-Maf mRNA in CD4(+) T lymphocytes cells were significantly elevated, the Blimp-1 mRNA in CD4(+) cells and PD-1 mRNA levels of Treg were lower in ITP patients in comparison with healthy controls; (4)The higher Plasma concentration of IL-21, and lower concentration of IL-2 were found in ITP patients.
CONCLUSION
(1)The lower proportion of Tfr cells and higher proportion of Tfh cells, as well as the abnormal ratio of Tfr/Tfh might account for the decreased platelet counts to be further involved in the immunological pathogenesis of children ITP; (2)The changes of plasma cytokines IL-2, IL-21 in microenvironment and the over-expression of Bcl-6 mRNA, c-Maf mRNA and the lower-expression of Blimp-1 mRNA in CD4(+) T cells, and over-expression of PD-1 mRNA in Treg cells might be account for the abnormal ratios of Tfr/Tfh cells in ITP patients.
目的
探讨滤泡调节性T细胞（Tfr）和滤泡辅助性T细胞（Tfh）在儿童免疫性血小板减少症（ITP）发病机制中的变化及作用。
方法
本研究纳入32例未经治疗的ITP患者及20例健康对照。采用流式细胞术检测循环Tfr和Tfh细胞比例；运用实时荧光定量PCR检测Bcl-6、c-Maf、Blimp-1及PD-1 mRNA转录因子和调节因子的表达；采用酶联免疫吸附测定法（ELISA）检测血浆白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）及白细胞介素-21（IL-21）浓度。
结果
（1）ITP患者Tfh细胞比例显著升高（P<0.05），而Tfr细胞及Tfr/Tfh细胞比值显著低于健康对照（P<0.05）；（2）相关性分析显示，Tfr细胞及Tfr/Tfh比值与血小板计数呈正相关，与血小板相关免疫球蛋白G（PA-IgG）水平呈负相关，而Tfh细胞比例与外周血PA-IgG水平呈正相关，与血小板计数呈负相关；（3）与健康对照相比，ITP患者CD4(+) T淋巴细胞中Bcl-6和c-Maf mRNA转录水平显著升高，CD4(+)细胞中Blimp-1 mRNA及调节性T细胞（Treg）中PD-1 mRNA水平降低；（4）ITP患者血浆IL-21浓度较高，IL-2浓度较低。
结论
（1）Tfr细胞比例降低、Tfh细胞比例升高以及Tfr/Tfh比值异常可能是导致血小板计数减少的原因，进一步参与儿童ITP的免疫发病机制；（2）血浆细胞因子IL-2、IL-21在微环境中的变化以及CD4(+) T细胞中Bcl-6 mRNA、c-Maf mRNA的过表达、Blimp-1 mRNA的低表达以及Treg细胞中PD-1 mRNA的过表达可能是ITP患者Tfr/Tfh细胞比值异常的原因。
Zotero 插件