未成熟树突状细胞诱导大鼠免疫低反应性  

Immune hyporesponsiveness induced by immature dendritic cells prolonged rat kidney allograft survival

作　　者：王翔[1] 赵鸿[1] 张元芳[1] 丁强[1] 瞿连喜[1] 吴忠[1] 孙正达[1] 古涛[1] 

机构地区：[1]复旦大学附属华山医院泌尿科,上海200040

出　　处：《中华器官移植杂志》2005年第4期203-206,共4页Chinese Journal of Organ Transplantation

基　　金：国家自然科学基金资助项目(30200262)教育部跨世纪优秀人才培养计划基金资助项目(2002-48)

摘　　要：目的观察供者来源的未成熟树突状细胞(imDCs)联合骨髓移植(BMT)对大鼠移植肾的保护作用,并探讨其机制。方法DA(RT1a)大鼠为供者,Lewis(RT1l)大鼠为受者,Wistar大鼠为无关第三品系。将实验动物随机分为5组,每组8只,进行不同的预处理后进行肾移植。(1)阴性对照组:受者不接受任何预处理;(2)imDCs诱导组:受者术前7d经尾静脉注射经60Co照射(30 Gy)灭活的、供者来源的未成熟树突状细胞2×107/只;(3)BMT诱导组:受者术前4 d经尾静脉注射供者来源的新鲜骨髓细胞2×108/只;(4)imDCs+BMT联合诱导组:受者术前7 d经尾静脉注射经60Co照射(30 Gy)灭活的、供者来源的未成熟树突状细胞2×107/只,术前4 d经尾静脉注射供者来源的新鲜骨髓细胞2×108/只;(5)第三品系组:预处理与imDCs+BMT联合诱导组相同,但供者肾脏来自Wistar大鼠。术后进行单向混合淋巴细胞反应(MLR);白细胞介素2(IL-2)逆转实验;体内细胞转移实验(DTH);流式细胞仪检测RT1a阳性细胞百分率。结果各组大鼠肾移植后平均存活时间分别为:阴性对照组(7.12±1.25)d;imDCs诱导组(24.38±3.20)d;BMT诱导组(7.87±2.10)d;第三品系组(6.63±1.06)d;而imDCs+BMT联合诱导组延长到(80.75±16.88)d;后者与上述4组比较,差异均有统计学意义(P<0.01)。免疫耐受的大鼠脾细胞增殖?Objective To study the effect of immature dendritic cells (imDC) transfusion in combination with bone marrow transplantation (BMT) on rat kidney allograft survival and its possible mechanism. Methods Renal allograft from DA rat was transplanted to Lewis rat. Forty recipient rats were randomized into 5 groups: (1) Negative control group; (2) imDC group: Lewis rats accepted imDC transfusion in the amount of 2× 107 only; (3) BMT group: Lewis rats accepted bone marrow transplantation in the amount of 2×108 only; (4) imDC + BMT group: Lewis rats accepted both imDC and BMC; (5)Third party donor group: Lewis rats accepted renal allograft from Wistar rats. One-way MLR was performed to assay splenic cell proliferation to allogeneic T cells. Exogenous IL-2 was added at the outset of another group as the former one-way MLR. Normal Lewis rat accepted splenic cells from tolerant rat in the amount of 1×108. DTH was assayed in the trans-tolerance model. Cells from spleen and thymus were harvested from recipient rats for detecting chimerism by flow cytometry. Results The median survival time (MST) of the renal allografts was (7. 12 ± 1. 25) days in negative control group, (24. 36 ± 3. 20)days in imDCs group and (7. 87 ± 2. 10)days in BMT group, respectively. In combined group, the MST was prolonged to (80. 75 ± 16. 88)days, which had significant difference as compared with the former three groups (P<0. 01). In the third party donor group, the MST was only (6. 63 ± 1. 06) days. MLR showed splenic cells derived from tolerant rat had weaker activity of proliferation than those from normal rats (3. 41 vs 7. 56, P<0. 01), but the hyporesponsiveness was partly reversed when exogenous IL-2 was added (3. 41 to 5. 85, P<0. 01). The trans-tolerance rats had a weaker DTH to donor cells than normal rats (0. 55 vs. 0. 93, P<0. 01). RT1a positive cells were detected in tolerant rats. The RT1a positive cells in splenic cells were (6. 21±0. 94) %, while in thymus cells were (2. 66 ±0. 77)%. Conclusions Combined use of imDC transfusion

关 键 词：未成熟树突状细胞 免疫低反应性 诱导大鼠 Wistar大鼠 单向混合淋巴细胞反应 ^60CO照射 尾静脉注射 流式细胞仪检测 LEWIS大鼠 供者来源 联合诱导 平均存活时间 免疫耐受 骨髓移植 骨髓细胞 阳性细胞 白细胞介素 脾细胞增殖 

分 类 号：R392.1[医药卫生—免疫学]