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预注射供体凋亡细胞对移植胰岛存活及外周血T淋巴细胞功能的影响

李双喜1,2,柳媛1,3,李宝雷1,3,杨树1,3,陈宏2,蔡德鸿1,2,张振2   

  1. 1.
    2. 南方医科大学珠江医院内分泌科
    3. 南方医科大学珠江医院
  • 收稿日期:2013-09-03 修回日期:2013-10-26 出版日期:2014-02-15 发布日期:2014-02-15
  • 通讯作者: 张振

The influences of pre-transfusion of donor apoptotic cells on survival of islet grafts and function of T lymphocytes

  • Received:2013-09-03 Revised:2013-10-26 Published:2014-02-15 Online:2014-02-15
  • Contact: ZHEN ZHANG

摘要: 目的: 研究凋亡细胞对胰岛移植大鼠外周血不同T细胞亚群细胞因子的影响,初步探寻凋亡细胞参与移植免疫耐受的途径和机制。方法: 利用课题组前期实验方法直线加速器照射来获取凋亡细胞。将接受移植的糖尿病大鼠随机分为四组,分别接受:生理盐水注射(A组)、正常细胞注射(B组)、凋亡细胞注射(C组)及坏死细胞注射(D组),各组在注射后1周给予同种异体胰岛移植。在胰岛移植前(即注射干预后1周)、胰岛移植后1周、2周以及排斥后,利用Luminex 100 Integrated System检测各组受体大鼠外周血不同T细胞亚群主要细胞因子IFN-γ、IL-10 的水平,酶联免疫方法测定TGF-β1水平。结果:C组大鼠外周血IFN-γ水平在移植前与其他各组无显著性差异,但在移植后7天、14天则明显低于其他各组 (P<0.050); 而IL-10 、TGF-β1水平在移植前、移植后7天及移植后14天均显著高于其他各组(P<0.050),排斥后这种差异消失。结论: 供体凋亡细胞预输注可使胰岛移植糖尿病大鼠血清IFN-γ明显降低,而显著升高IL-10 、TGF-β1水平,提示凋亡细胞可能通过调节不同T细胞亚群(Th1/Th2、Th3)之间的动态平衡来参与胰岛移植免疫耐受的诱导。

关键词: 凋亡, 胰岛移植, T淋巴细胞, 免疫调节

Abstract: Objective : To study the influence of apoptotic cells on the cytokines of different subsets of T cell in the peripheral blood from the recipient rats after islet transplantation in order to explore the possible way of apoptotic cells involved in the reducing of immune tolerance. Methods: apoptotic cells from the donor rats were obtained by irradiation of X-irradiation from electron linear accelerator. the diabetic rats for islet transplantation were randomly divided into four groups:each group were respectively injected by Physiological saline (A group), normal cells(B group), apoptotic donor cells(C group), and necrotic donor cells(D group). then, each group rats received islet transplantation on the seventh day after the pre-injection. The level of cytokines IFN-γ、IL-10 in peripheral blood were determined by Luminex 100 Integrated System and TGF-β1 measured by ELISA respectively at 0d, 1week, 2week after islet transplantation. Results:: The level of IFN-γ of C group has no difference before transplantation, but at 7d, 14d after transplantation it is significantly lower than other groups(P<0.050). The content of IL-10 and TGF-β1 in C group has a significant increase compared with other three groups(P<0.050)before transplantation and at 7d , 14d after transplantation, the difference disappeared after rejection. Conclusions: We have demonstrated that the pre-treatment of donor apoptotic cells can decrease the level of IFN-γ and increase the level of IL-10 and TGF-β1. All these would indicate that the transfusion of apoptotic cells might induce the immune tolerance by accommodating the balance of Th1/Th2、Th3.

Key words: Apoptosis, islet transplantation, T lymphocytes, immune regulation