过继性转移TGF-β诱导CD4^+CD25^+调节性T细胞对自然流产模型小鼠胚胎丢失率的影响  

Effects of CD4^+CD25^+ regulatory T cells induced by adoptive transfer of TGF-β on rate of embryo loss of spontaneous abortion mice model

作　　者：邱添[1] 滕银成[1] 徐亮[1] 

机构地区：[1]上海交通大学附属第六人民医院妇产科,上海200233

出　　处：《上海交通大学学报（医学版）》2014年第8期1120-1125,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金青年项目(81100474)~~

摘　　要：目的观察过继性转移转化生长因子-β(TGF-β)诱导生成CD4+CD25+调节性T细胞对自然流产模型小鼠胚胎丢失率的影响。方法从正常妊娠CBA/J孕鼠脾脏中分选CD4+CD25-T细胞,体外经TGF-β诱导转化为CD4+CD25+调节性T细胞,流式细胞仪检测其对自身反应性T细胞增殖的抑制作用。实验小鼠随机分为正常妊娠组和自然流产模型组,后者根据干预方式的不同分为空白组(自然流产模型未干预)、CD4+CD25+T细胞组(自然流产模型过继性转移天然CD4+CD25+调节性T细胞)、TGF-β诱导CD4+CD25+T细胞组(自然流产模型过继性转移TGF-β诱导CD4+CD25+调节性T细胞)和对照组(自然流产模型注射CD4+CD25-T细胞)。于孕第14日采集血样后处死小鼠。ELISA法检测血清白介素-10(IL-10)、TGF-β1和γ干扰素(IFN-γ)水平,Western blotting和Real-time PCR检测蜕膜组织Foxp3 mRNA和蛋白的表达。计算各组孕鼠胚胎丢失率。结果与空白组和对照组比较,天然CD4+CD25+T细胞组和TGF-β诱导CD4+CD25+T细胞组血清IL-10、TGF-β1水平升高,IFN-γ水平降低;蜕膜组织中Foxp3 mRNA和蛋白的表达上调;胚胎丢失率显著降低(P<0.05)。结论向自然流产模型小鼠过继性转移TGF-β诱导生成CD4+CD25+调节性T细胞,可诱导小鼠体内Th1/Th2免疫反应向Th2优势偏移,降低胚胎丢失率。Objective To observe the effects of CD4 ＋ CD25 ＋ regulatory T （Treg） cells induced by adoptive transfer of transforming growth factor- β （ TGF- β） on the rate of embryo loss of mice of the spontaneous abortion model. Methods CD4 ＋ CD25＋ cells were isolated induced to CD4 ＊CD25＋ Treg cells by TGF-β /n vitro. from the spleen of normal pregnant CBA/J mice and The inhibit effect of TGF-β induced Treg cells on the proliferation of self-reactive T cells was measured by the flow cytometry. The CBA/J mice were randomly divided into the normal pregnancy group and spontaneous abortion group. The latter was further divided into the blank group （ spontaneous abortion model without intervention）, innate CD4 ＋ CD25 ＋ T cells group （ spontaneous abortion model with adoptive transfer of innate CD4 ＋ CD25 ＋ Treg cells）, TGF- β induced CD4 ＋ CD25 ＋ T ceils group （ spontaneous abortion model with adoptive transfer of CD4 ＋ CD25 ＋ Treg cells induced by TGF-β）, and control group （spontaneous abortion model with injection of CD4＋ CD25＋ T cells） according to the intervention method. On day 14 of pregnancy, the mice were sacrificed and the blood samples were gathered. The levels of serum IL-10, TGF-a, and IFN-β were measured by the ELISA. The expressions of Foxp3 mRNA and protein in deciduas tissues were measured by the Western blotting and Real-time PCR. The rate of embryo loss of each group was calculated. Results Compared to the blank group and control group,the levels of serum IL-10 and TGF-β1 of the innate CD4＋ CD25 ＋T cells group and TGF-β induced CD4＋ CD25 ＋T cells group increased; the level of serum IFN-β; the expressions of Foxp3 mRNA and protein in deciduas tissues increased; and the rate of embryo loss significantly decreased （P 〈 0.05）. Conclusion CD4 ＋CD25 ＋ Treg cells induced by adoptive transfer of TGF-β for mice of the spontaneous abortion model can induce Thl and Th2 immune responses towards Th2 and decrease the rate of embryo loss.

关 键 词：自然流产 过继性转移 转化生长因子-Β CD4+CD25+调节性T细胞 FOXP3 

分 类 号：R714.21[医药卫生—妇产科学]