CD4^+CD25^+Foxp3^+调节性T细胞的体外扩增及其在移植物抗宿主病中的应用  

Expansion of CD4^+CD25^+Foxp3^+ regulatory T cells in vitro and application in graft-versus-host disease

作　　者：丰涛[1,2] 杨洁[2] 范华骅[2] 

机构地区：[1]华东师范大学生命科学学院生物医学系,上海200062 [2]上海市血液中心血液工程研究室,上海200051

出　　处：《生命科学》2009年第1期56-61,共6页Chinese Bulletin of Life Sciences

基　　金：上海市科委基金(05XD14029)

摘　　要：同种异基因造血干细胞移植是急、慢性白血病及其他恶性血液病重要的治疗方法,但急慢性移植物抗宿主病(graft-versus-host disease,GVHD)作为异基因造血干细胞移植的主要并发症严重影响移植患者的存活率,阻碍移植的临床推广。很多研究发现,高表达Foxp3的CD4+CD25+调节性T细胞(regulatory T cells,Treg)不仅能控制急慢性GVHD的发生,而且不影响移植物抗白血病效应(graft-versus-leukemia,GVL),在急慢性GVHD发生发展及治疗方面有重要的作用。但Treg细胞在体内的数量很少,不能满足临床应用需求。目前应用外源的IL-2联合TCR、CD28信号通路共同刺激以及运用树突状细胞(dendritic cell,DC)刺激均能达到体外有效扩增Treg细胞的目的。这些扩增的Treg细胞在控制造血干细胞移植过程中急慢性GVHD的发生及防治自身免疫性疾病和移植排斥等方面具有明显作用,在疾病控制和临床应用中具有广阔前景。Allogeneic hematopoietic stem cell transplantation is an important way to control acute and chronic leukemia and other hematological malignancies, but acute and chronic graft-versus-host diseases （GVHD）, which are major complications in the allogeneic hematopoietic stem cell transplantation influence the survival rate severely, and restrict the clinical application of transplantation. A great number of studies found that CD4^＋CD25^＋ regulatory T cells（Treg cell） expressing Foxp3 highly are potential in controlling acute and chronic GVHD, and do not weaken graft versus leukemia（GVL）. It plays an important role in acute and chronic GVHD generation, development and therapy. However, the proportion of Treg cell in vivo is very small, so it can not meet the clinical requirements. At present, most experiments utilize exogenous IL-2 and TCR, CD28 signaling pathway to expand Treg cells in vitro. In addition, dendritic cells can induce Treg cells proliferation effectively in vivo and in vitro. These expended Treg cells exert significant effect in control acute and chronic GVHD, as well as the prevention and suppression of autoimmune diseases and transplant rejection, and have broad prospects in disease control and clinical application.

关 键 词：CD4^+CD25^+FOXP3^+调节性T细胞 移植物抗宿主病 树突状细胞 

分 类 号：R392.4[医药卫生—免疫学]