中国实用儿科杂志

中国实用儿科杂志

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泼尼松治疗原发性肾病综合征对患儿CD4+CD25+调节性T细胞的影响分析

杨　军， 李成荣， 黄惠君， 祖　颖， 王国兵， 李永柏， 张　蕾   

  1. 深圳市儿童医院免疫肾脏科，广东深圳　518026
  • 收稿日期:2008-09-10 修回日期:2009-01-05 出版日期:2009-05-06 发布日期:2010-03-01

Influence of prednisone on CD4+CD25+ regulatory T cell in children with primary nephrotic syndrome.

YANG Jun， LI Cheng-rong，HUANG Hui-jun， ZU Ying，WANG Guo-bing，LI Yong-bai，ZHANG Lei.   

  1. Shenzhen Children’s Hospital ， Shenzhen 518026， China
  • Received:2008-09-10 Revised:2009-01-05 Online:2009-05-06 Published:2010-03-01

摘要： 目的　观察原发性肾病综合征（PNS）患儿泼尼松治疗前后CD4+CD25+ 调节性T细胞（CD4+CD25+ Tr）的变化，阐明肾上腺糖皮质激素治疗儿童PNS的免疫机制。方法　选择2004—2007年在深圳市儿童医院住院治疗的初发PNS患儿42例，其中激素敏感型32例，激素耐药型10例。同期25例健康体检儿童作为对照组。流式细胞术检测泼尼松治疗前后外周血CD3+CD4+CD8-、CD3+CD4-CD8+、CD4+CD25+Tr的比例，荧光定量聚合酶链反应（Real-time PCR）检测泼尼松治疗前后外周血单个核细胞（PBMC）叉头型基因P3（Foxp3）、细胞毒性T淋巴细胞相关抗原4（CTLA-4）和糖皮质激素诱导的肿瘤坏死因子受体 （GITR）基因mRNA的表达。结果 　与对照组比较，PNS患儿外周血CD3+CD4+CD8- T细胞、CD3+CD4-CD8+ T细胞、CD4+CD25+ Tr比例无明显改变（P > 0.05）。激素敏感型PNS患儿CD4+CD25+Tr比例在泼尼松治疗后明显增高，差异有统计学意义（P < 0.01）；激素耐药型PNS患儿CD4+CD25+Tr比例在泼尼松治疗前后无明显改变（P > 0.05）。激素敏感型PNS患儿在泼尼松治疗后PBMC细胞Foxp3、CTLA-4和GITR基因mRNA的表达明显增高；而激素耐药型PNS患儿泼尼松治疗前后Foxp3、CTLA-4基因表达无明显改变，仅GITR表达明显增高。 结论 泼尼松等肾上腺糖皮质激素类药物可通过上调激素敏感型PNS患儿CD4+CD25+调节性T细胞的表达发挥免疫治疗作用。

关键词: 原发性肾病综合征, 糖皮质激素, 调节性T细胞, Foxp3

Abstract: Objective 　To study the changes of CD4+CD25+ Tr in primary nephrotic syndrome before and after treatment with prednisone.To explore the immuno-pathogenesis in children with primary nephrotic syndrome. Methods　A total of 42 patients with PNS in Shenzhen Children's Hospital from 2004 to 2007 were divided into the steroid-responsive group （32 cases） and the steroid-resistant group（10 cases）， and 20 age-matched healthy subjects were studied. Before and after treatment ，flow cytometric analysis （FCM） was performed to detect the percentage of T cells subpopulation （including CD3+CD4+CD8-，CD3+CD4-CD8+、CD4+CD25+Tr） ； real-time PCR was used to detect Foxp3 ， CTLA-4 and GITR mRNA expression in peripheral blood mononuclear cell （PBMC）.Results　Compared with healthy control subjects ， the percentage of CD3+CD4+CD8- T cell ， CD3+CD4-CD8+ T cell and CD4+CD25+ Tr cell in patients with PNS had no change . The percentage of CD4+CD25+Tr of the steroid-responsive group was significantly higher after treatment with prednisone than before（P < 0.01）. The percentage of CD4+CD25+Tr of steroid-resistant group had no change before and after treatment（P > 0.05）. At the same time， after treatment ，the Foxp3 ， CTLA-4 and GITR mRNA expression in PBMC were significantly higher in the steroid-responsive group， while in the steroid-resistant group the Foxp3 ， CTLA-4 mRNA expression had no change， and only GITR mRNA expression was significantly higher. Conclusion　The glucocoticoid drugs （including prednisone） might perform immunotherapy effect through upregulating CD4+CD25+ Tr gene expression in steroid-responsive children with PNS.

Key words: Foxp3 , glucocoticoid , regulatory T cell