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

YANG JunLI Cheng-rongHUANG Hui-junZU YingWANG Guo-bingLI Yong-baiZHANG 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

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

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

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