雷帕霉素诱导致耐受性树突状细胞的实验研究  

Use of rapamycin in the induction of tolerogenic dendritic cells in vitro

作　　者：杨晓勇[1] 张小东[1] 高居忠[1] 

机构地区：[1]首都医科大学附属北京朝阳医院泌尿外科,北京100020

出　　处：《中华细胞与干细胞移植（电子版）》2010年第1期16-19,共4页

摘　　要：目的观察雷帕霉素对小鼠骨髓来源的树突细胞（DC）分化、成熟和功能的影响,阐述其诱导免疫耐受的可能机制。方法在小鼠骨髓来源的DCp培养过程中加入粒细胞-巨噬细胞集落刺激因子（GM-CSF）,白介素-4（IL-4）和雷帕霉素,用流式细胞仪检测各组DC表面CD11c,CD40和CD80的表达。MTT比色法行体外混合淋巴细胞反应（MLR）观察每组对同种T细胞的刺激增殖能力。结果雷帕霉素显著抑制了外源刺激下DCp的成熟过程,抑制其表面共刺激分子（CD40,CD80）的表达,并显著抑制其同种T细胞激活能力（P〈0.01）。结论雷帕霉素通过显著抑制DCp的成熟,诱导产生致耐受性树突细胞（Tol-DC）,同时促进调节性T细胞（Treg）的生成,从而在移植物受者导致供着特异性的免疫耐受。Objective To investigate the effect of Rapamycin on the differentiation, maturation and function of murine bone marrow derived dendritic cells in vitro and to explore the possible mechanism of tolerance induction. Methods DC progenitors were propagated from mouse bone marrow with granulocyte-macrophage colony-stimulating factor（GM-CSF） plus IL-4 for 6 days in the presence or absence of RAP （20 ng/ml） . During DC culture, morphology of cell was observed under electronmicroscopy. Cell surface expression of CD11c, CD40 and CD80 was analyzed by flow cytometry. The antigen-presenting function of DC was determined in one-way mixed leukyocyte reactions. Results The immunopheno-typic analysis showed that in comparison with those in the control group and the LPS group the expression of the costimulatory molecules CD40 and CD80 were significantly lower in the Rap-group and Rap＋LPS group. The ability to stimulate proliferation of T cells of the same genotype in the Rap-group was significantly inhibited （P 0.01）. Conclusion Rap has a significant suppressive effect on the maturation and function of DCs, which genetrated Tol-DC. On the other hand, Tol-DCs possessed an ability to generate Treg cells in vitro. The present study highlights the therapeutic potential of preventing allograft rejection using in vitro- generated Tol-DCs and Treg.

关 键 词：致耐受性树突细胞 调节性T细胞 移植耐受 免疫调节 

分 类 号：R593.2[医药卫生—内科学]