程序性死亡因子配体1修饰供者DC对大鼠异体胰岛移植存活的影响

Influence of dendritic cells modified with PDL1 on the survival of pancreatic islets allografts in rats

目的探讨共刺激信号阻断剂PDL1基因修饰的树突状细胞(dendritic cells,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PDL1(程序性死亡因子配体1)基因重组腺病毒转染供、受体骨髓源性DC使之表达PDL1;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1、组2),供、受体DC混合后注入受体(组3),注射生理盐水的为空白对照组(组4);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1和组3血糖维持正常时间和受体存活时间显著延长〔组1:(22.47±11.72)d和(41.25±12.98)d,P<0.01;组3:(37.67±14.71)d和(52.31±15.47)d,P<0.001)〕差异有统计学意义,组2移植胰岛存活时间无延长〔(3.75±1.33)d与(7.33±1.97)d,P>0.05〕差异无统计学意义。术后第20天,组1、组3脾细胞对供体抗原刺激的反应均明显低于正常对照(0.27±0.08和0.23±0.06与0.70±0.09,P<0.001),而对无关抗原刺激的反应与正常对照差异无统计学意义(0.66±0.07和0.66±0.07与0.69±0.05,P>0.05)。结论PDL1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 influence of donor and the recipient dendritic cells（DCs） modified with PDL1 on the survival of pancreatic islets allografts in rats. Methods Bone marrow derived Des of Lewis and Brown Norway（BN） rats were modified with PDL1 gene recombined adenovirus and injected into Lewis rats 24h before BN→Lewis pancreatic islets transplantation alone （Group 1, donor DCs; Group 2, recipient DCs） and in combination （Group 3, donor and recipient DCs）. Time of maintaining blood glycose level and survival time of pancreatic islets allografts was observed and one-way mixed splenic cell reaction （MSR） of the recipients to donors and the third party rats were performed by means of MTT on the 20th postoperative day. Results Time of maintaining blood glycose level and survival time of pancreatic islets allografts in group 1 and group 3 was prolonged significantly （compared with control,（22.47±11.72）d and （41.25±12.98）d,P〈0.01;（37.67±14.71）d and （52.31±15.47）d,P〈0. 001 respectively] and no evidence of prolonging time of maintaining blood glycose level and survival time was observed in group 2（（8.75 ±3.33）d vs （7.33±1.97）d,P〉0.05）3. On 20d, the recipients in group 1 and group 3 showed significant hyporesponsiveness to donors （compared with normal control, MSR was 0. 27±0.08 and 0. 23 ± 0. 06 vs 0. 70±0.09,P〈0. 001 respectively） while showed normal reaction to the third party. Conclusion Donor DCs modified with PDL1 could induce a significant prolongation of time of maintaining blood glycose level and survival time of pancreatic islets allografts and the administration of both donor and recipient DCs modified with PDL1 could induce a longer survival of pancreatic islets 1 allografts.