霉酚酸酯诱导Balb/c小鼠调节性T细胞的分化和增殖  

Mycophenolate mofetil promotes differentiation and proliferation of mouse CD4+CD25+ regulatory T cells

作　　者：龚淑文[1] 杨梅[1] 张岩[1] 庄垟垟[1] 杨亦荣[1] 郑少玲[1] 

机构地区：[1]温州医学院附属第一医院移植中心,325000

出　　处：《实用医学杂志》2011年第6期967-970,共4页The Journal of Practical Medicine

基　　金：浙江省自然科学基金资助项目(编号:Y206924)

摘　　要：目的:观察霉酚酸酯对Balb/c小鼠调节性T细胞(regulatory T cells,Treg)分化和增殖的影响,进一步探讨其可能的免疫耐受诱导机制。方法:取8周龄的SPF级Balb/c小鼠24只,随机分为3组,霉酚酸酯组(MMF组):每只灌胃霉酚酸酯40mg/(kg·d),环孢素组(CsA组):每只灌胃CsA10mg/(kg·d),对照组:灌胃每天予等体积生理盐水。3周后眼眶静脉取血,无菌条件下分离脾脏,制备单细胞悬液。采用流式细胞仪检测小鼠外周血和脾细胞CD4+CD25+Treg细胞,免疫组化法检测小鼠脾脏Foxp3蛋白的表达。结果:霉酚酸酯组小鼠外周血和脾细胞中CD4+CD25+Treg细胞的比例分别为(6.35±0.09)%和(11.62±1.10)%,CsA组小鼠外周血和脾细胞中CD4+CD25+Treg细胞的比例分别为(2.57±0.09)%和(5.46±0.75)%,对照组小鼠外周血和脾细胞中CD4+CD25+Treg细胞的比例分别为(4.64±0.13)%和(7.61±0.73)%,差异均有显著性(P<0.01)。霉酚酸酯组小鼠脾脏Foxp3蛋白的表达水平明显高于对照组,差异有显著性(P<0.01),CsA组小鼠脾脏Foxp3蛋白的表达水平明显低于对照组。结论:霉酚酸酯能够明显诱导Balb/c小鼠体内CD4+CD25+Treg细胞的增殖,并能提高Foxp3蛋白的表达,有利于免疫耐受的形成,其免疫抑制机制与CsA不同。Objective To analyze the influence of mycophenolate mofetil on the differentiation and proliferation of CD4＋CD25＋Treg cells, and reveal its possible role in inducing immune tolerance. Methods Twenty-four 8-week-old SPF Balb/e mice were randomly divided into three groups, mycophenolate mofetil group （MMF）, cyclosporine group （CsA） and sham group. They were intraperitoneally administrated with mycophenolate mofeti140 mg/（kg-d）, CsA 10 mg/（kg·d） and same volume saline respectively. After three weeks, orbital vein blood was collected and spleen cells suspension were prepared. Flow cytometry was used to determine the proportions of CD4＋ CD25＋Treg cells,and the expression of Foxp3 protein in spleen was analyzed by immunochemistry. Results The CD4＋CD25＋Treg cells of peripheral and spleen were （6.35± 0.09）% and （11.62 ±1.10）% in MMF group, （2.57 ± 0.09）% and （5.46 ± 0.75）% in CsA group, （4.64 ± 0.13）% and （7.61 ± 0.73）% in Sham group respectively. There were significant differences among these three groups （P 〈 0.01 ）. Immunochemlstry analysis showed that compared to the sham group, the expression of Foxp3 protein in CsA group decreased significantly （P 〈 0.01 ）, while its expression in MMF group increased significantly（P 〈 0.01 ）. Conclusion MMF promotes the proliferation of CD4＋CD25＋Foxp3＋Treg cells in vitro,and facilitates the development of immne tolerance. And its immune suppression mechanism is different from that of eyclosporine A.

关 键 词：T淋巴细胞 调节性 霉酚酸酯 环孢素A FOXP3 细胞分化 细胞增殖 

分 类 号：R96[医药卫生—药理学]