诱导性调节性T细胞抑制移植排斥反应的作用研究  

Suppressive Function of Induced Regulatory T Cells in Allograft Rejection

作　　者：刘甜[1] 苏映军[1] 陈晨[1] 陈建武[1] 刘蓓[1] 杨阳[1] 张栋梁[1] 郭树忠[1] 

机构地区：[1]第四军医大学西京医院整形外科研究所,陕西西安710032

出　　处：《现代生物医学进展》2014年第25期4826-4831,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金重点项目(30830102);国家自然科学基金面上项目(81071581)

摘　　要：目的:通过体外诱导的方法将幼稚CD4+T细胞(na觙ve CD4+T cell)转化为调节性T细胞(RegulatoryT cells,Tregs),并验证其在小鼠异体皮片移植模型上对移植排斥反应的抑制作用。方法:分选na觙ve CD4+T细胞并在体外诱导其转化为Tregs,流式检测细胞确定其转化率。将诱导性Treg(induced Treg,iTreg)与效应T细胞(Effective T cells,Teffs)以不同比例共同培养检测其对T细胞增殖的抑制能力。建立C57bl/6到Balb/c小鼠的异体皮片移植模型,植皮术后将iTreg经由股静脉输注入受体(Balb/c小鼠)体内,观察皮片存活情况,绘制皮片存活曲线。同时于皮片移植术后11天对皮片进行病理切片,观察移植排斥反应状况。结果:体外诱导na觙ve CD4+T细胞转化为iTreg的比例约44%,在iTreg:Teff比例大于1:4时,iTreg具有明显地抑制Teff增殖的作用,且这种抑制作用具有剂量依赖性。植皮小鼠输注iTreg后皮片存活时间较对照组延长约2.4天,病理切片显示排斥反应减轻,但皮片在14天左右时仍被排斥。结论:体外诱导的iTreg能够在体外抑制Teff增殖,且能有效抑制小鼠异体皮片移植后排斥反应。Objective： Induced regulatory T cells （iTregs） have been implicated in maintaining peripheral immune tolerance. This study aims to test whether iTregs could suppress allograft rejection in a skin allograft model. Methods： Naive CD4＋ T cells were purified from naive mice splenocytes and induced in vitro by culturing with anti-CD3/CD28-coated Dynalbeads, and supplemented with interleukin（IL）-2 and transforming growth fator（TGFI3）. Suppressive ability of iTregs was assayed by co-culturing with CD4＋CD25-T cells （Teffs） in vitro and by allogeneic skin transplantation in vivo. Results： Flow cytometry showed the percentage of CD4＋CD25 ＋ Foxp3＋ cells in induced cells were approximately 44%. iTregs exerted suppressive function when cocultured with Teffs in vitro and prolonged fully MHC-mismatehed skin graft survival. Conclusions： iTreg cells show suppressive function both in vitro and in vivo, but iTreg cells alone can not induce immune tolerance.

关 键 词：调节性T细胞 细胞培养 移植排斥反应 

分 类 号：Q95-3[生物学—动物学] R393[医药卫生—基础医学]