树突状细胞共刺激分子表达与免疫抑制剂的干预  

Dendritic cell costimulatory molecule expression and immunosuppressant intervention

作　　者：杨晓勇[1] 姚庆春[2] 王玮[1] 齐曼[1] 洪希莹 刘晨妹 尹航[1] 刘航[1] 任亮[1] 胡小鹏[1] 张小东[1] 

机构地区：[1]首都医科大学附属北京朝阳医院泌尿外科,北京市100020 [2]山东大学附属省立医院重症医学科,山东省济南市250021

出　　处：《中国组织工程研究》2015年第24期3876-3881,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金专项基金(81050014)~~

摘　　要：背景:以往关于器官移植免疫抑制和抗排斥反应的研究,多关注T淋巴细胞介导的免疫反应及免疫抑制剂对T淋巴细胞的作用,树突状细胞作用尚不清楚,且对于免疫抑制剂对树突状细胞影响的表现及机制亦不尽相同。目的:比较不同免疫抑制剂对树突状细胞共刺激分子表达及功能的影响,探讨其免疫抑制作用机制。方法:在诱导C57BL/6小鼠骨髓细胞定向分化为树突状细胞时分别加入20μg/L雷帕霉素、0.04 mg/L霉酚酸酯、10μg/L他克莫司和1 mg/L环孢霉素A。结果与结论:流式细胞仪检测结果显示,各组CD40表达为:雷帕霉素<他克莫司<环孢霉素A<霉酚酸酯(P<0.01);CD86表达分别为:雷帕霉素<他克莫司<环孢霉素A=霉酚酸酯(P<0.01);CD80、CD11c及主要组织相容性复合体Ⅱ的表达各组差异无显著性意义(P>0.05)。单向混合淋巴细胞反应结果显示,各组树突状细胞共刺激T细胞增殖能力表现为:雷帕霉素<霉酚酸酯<他克莫司=环孢霉素A(P<0.05)。结果证实,雷帕霉素、他克莫司、环孢霉素A、霉酚酸酯均通过抑制树突状细胞共刺激分子CD40及CD86表达而发挥免疫抑制作用,以雷帕霉素最为显著;虽然以上药物对树突状细胞抗原递呈能力主要组织相容性复合体Ⅱ的表达均无明显抑制性,但均能抑制树突状细胞刺激T细胞增殖的能力,雷帕霉素的抑增殖能力最强。BACKGROUND： Previous studies on immunosuppression and anti-rejection after organ transplantation mainly focused on effects of T lymphocytes-mediated immune response and immunosuppressive agents on T lymphocytes. Effects of dendritic cells were unclear. The manifestation and mechanism of immunosuppressive agent effects on dendritic cells are not identical. OBJECTIVE： To compare the effects of different immunosupprassive agents on expression and function of costimulatory molecules of dendritic cells, and to explore the mechanism of action of immunosuppressive agents, METHODS： 20 pg/L rapamycin, 0.04 mg/L mycophenolate, 10 pg/L tacrolimus and 1 mg/L cyclosporine A were separately added during bone marrow cells of C57BL/6 mice were differentiated into dendritic cells. RESULTS AND CONCLUSION： Flow cytometry results revealed that CD40 expression in each group： rapamycin 〈 tacrolimus 〈 cyclosporine A 〈 mycophenolate mofetil （P 〈 0.01）; CD86 expression： rapamycin 〈 tacrolimus 〈 cyclosporine A = mycophenolate mofetil （P 〈 0.01）. There was no significant difference in CD80, CD1 lc and major histocompatibility complex II expression among groups （P 〉 0.05）. One-way mixed lymphocyte reaction results displayed dendritic cell costimulatory T cell proliferation in each group： rapamycin 〈 mycophenolate mofetil 〈 tacrolimus = cyclosporine , （P 〈 0.05）. The results confirmed that rapamycin, tacrelimus, cyclosporine A, and mycophenolate mofetil exerted immunosuppression by sup.pressing CD40 and CD86, especially rapamycin. Above medicines do not noticeably inhibit major histocompatibility complex II expression, but suppress T cell proliferation, and the inhibitory effect of rapamycin on cell proliferation is strongest.

关 键 词：组织构建 组织工程 树突状细胞 共刺激分子 雷帕霉素 免疫抑制剂 混合淋巴细胞反应 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]