中华医学杂志(英文版)2004,Vol.117Issue(8):1184-1189,6.
Transplantation tolerance mediated by regulatory T cells in mice
Transplantation tolerance mediated by regulatory T cells in mice
摘要
Abstract
Background With potent suppressive effect on responder T cells, CD4+CD25+ regulatory T (Treg) cells have become the focus of attention only recently and they may play an important role in transplantation tolerance. However, the mechanism of action is not clear. This study was designed to assess the possibility of using CD4+CD25+ Treg cells to induce transplantation tolerance and to investigate their mechanism of action.Methods CD4+CD25+ Treg cells were isolated using magnetic cell separation techniques. Mixed lymphocyte reactions were used to assess the ability of Treg cells to suppress effector T cells. Before skin transplantation, various numbers of CD4+CD25+Treg cells, which have been induced using complex skin antigens from the donor, were injected into the host mice either intraperitoneally (0.5×105, 1×105, 2×105, 3×105, 4×105, or 5×105) or by injection through the tail vein (5×103, 1×104, 2×104, 5×104, 1×105, 2×105). Skin grafts from two different donor types were used to assess whether the induced Treg cells were antigen-specific. The survival time of the allografts were observed. Single photon emission computed tomography was also used to determine the distribution of Treg cells before and after transplantation.Results Treg cells have suppressive effect on mixed lymphocyte reactions. Grafts survived longer in mice receiving CD4+CD25+ Treg cell injections than in control mice. There was a significant difference between groups receiving intraperitoneal injection of either 2×105 or 3×105 CD4+CD25+Treg cells and the control group (P<0.05, respectively). Better results were achieved when Treg cells were injected via the tail vein than when injected intraperitoneally. The transplantation tolerance induced by CD4+CD25+ Treg cells was donor-specific. Analysis of the localization of Treg cells revealed that Treg cells mainly migrated from the liver to the allografts and the spleen.Conclusions CD4+CD25+Treg cells can induce donor-specific transplantation tolerance. Cell-to-cell contact may be the primary mechanism by which Treg cells act on effector T cells.关键词
T-lymphocytes/immune tolerance/skin transplantation/lymphocyte culture test, mixedKey words
T-lymphocytes/immune tolerance/skin transplantation/lymphocyte culture test, mixed分类
医药卫生引用本文复制引用
冯宁翰,吴宏飞,吴军,张炜,眭元庚,贺厚光,张春雷,郑峻松..Transplantation tolerance mediated by regulatory T cells in mice[J].中华医学杂志(英文版),2004,117(8):1184-1189,6.基金项目
This work was supported by grants from the National Natural Science Foundation of China (No.30200264) and the Key Project of the National Natural Science Foundation of China (No.39993430-2). (No.30200264)