CTLA4Ig转染供者DC对同种异体胰岛移植存活的影响

Effect of dendritic cells modified with B7 blocking agent CTLA-4Ig on survival of pancreatic islets allografts in rats

目的探讨共刺激信号阻断剂CTLA-4Ig基因修饰的树突状细胞(dendriticcells,DC)对胰岛移植存活的影响。方法以BN、Lewis大鼠为胰岛移植供、受体;用CTLA-4Ig基因重组腺病毒转染供、受体骨髓源性DC使之表达CT-LA-4Ig;将供、受体DC于胰岛移植前24h经股静脉分别注入受体(设为组Ⅰ、组Ⅱ),供、受体DC混合后注入受体(组Ⅲ),注射生理盐水的为空白对照组(组Ⅳ);观察各组糖尿病鼠高血糖改善情况及存活时间,术后第20天,MTT法检测受体脾细胞对供体及无关抗原刺激的反应。结果与对照组相比,组Ⅰ和组Ⅲ血糖维持正常时间和受体存活时间显著延长[组Ⅰ:(28.75±13.60)d和(35.38±13.21)d,P<0.01;组Ⅲ:(41.25±13.74)d和(49.50±13.87)d,P<0.01],组Ⅱ移植胰岛存活时间无延长[(8.75±3.33)d与(7.33±1.97)d相比,P>0.05]。术后第20天,组Ⅰ、组Ⅲ脾细胞对供体抗原刺激的反应均明显低于正常对照[(0.24±0.05)和(0.21±0.05)与(0.70±0.09)相比,P<0.01],而对无关抗原刺激的反应与正常对照无显著差异[(0.66±0.07)和(0.66±0.07)与(0.69±0.05)相比,P>0.05]。结论CTLA-4Ig基因修饰的供体DC可以明显延长大鼠移植胰岛的存活时间,而受体DC则无此作用,但两种DC联合应用可以使移植胰岛获得更长的存活时间。

Objective To study the effect of donor and recipient dendritic ceils （DCs） modified with B7 blocking agent CTLA-4Ig on the survival of pancreatic islets allografts in rats. Methods Bone marrow derived DCs of Lewis and Brown Norway （BN） rats were modified with CTLA-4Ig gene recombined adenovirus and injected into Lewis rats 24 h before BN to Lewis pancreatic islets transplantation alone （donor DCs in Group Ⅰ , recipient DCs in Group Ⅱ ） and in combination （ donor and recipient DCs in Group Ⅲ ）. Time of maintaining blood glycose level and survival time of pancreatic islets allografts were observed and one-way mixed splenic cell reaction （MSR） of the recipients to donors and the third party rats were performed by MTT on postoperative day 20. Results Time of maintaining blood glycose level and survival time of pancreatic islets allografts in Group Ⅰ and Group Ⅲ were prolonged significantly as compared with control [28.75 ± 13.60） d and （35.38 ± 13. 21） dinGroup Ⅰ , （41.25 ±13.74） dand（49.50±13.87） dinGroup m, （1.33 ±1.97） dand（7.33± 1.97） d in control group], but showed no significance in Group Ⅱ and control group [（8.75 ±3.33） d and 7.33 ± 1.97 d in Group Ⅱ ]. On postoperative day 20, the recipients in Group Ⅰ and Group Ⅲ showed significant hyporesponsiveness to donors [MSR was （0.24 ±0.05） and （0.21 ±0.05） in Group Ⅰ and Ⅲ, vs （0. 70 ± 0. 09） in normal control, P 〈 0.001 ], but showed normal reaction to the third party. Conclusion Donor DCs modified with CTLA-4Ig could induce a significant prolongation of maintaining blood glycose level and survival time of pancreatic islets allografts, and the administration of both donor and recipient DCs modified with CTLA-4Ig could induce a longer survival of pancreatic islets allografts.