PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.
PD-L1 Deficiency within Islets Reduces Allograft Survival in Mice.
复制标题
胰岛内 PD-L1 缺乏会降低小鼠同种异体移植物的存活率
DOI：
10.1371/journal.pone.0152087
复制
发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Yang J
中科院分区：
文献类型：
--
作者：
Ma D;Duan W;Li Y;Wang Z;Li S;Gong N;Chen G;Chen Z;Wan C;Yang J
背景胰岛移植有望治愈1型糖尿病(T1 DM)。然而，免疫排斥反应，特别是由同种异体反应性T细胞反应引起的免疫排斥反应，仍然是移植胰岛长期存活的制约因素。程序性死亡配体-1(PD-L1)是一种负性共刺激分子。供者心脏中PD-L1缺乏会加速同种异体移植排斥反应。在这里，我们调查供体胰岛PD-L1缺乏是否会缩短同种异体移植物存活时间。方法采用葡萄糖刺激试验评价PD-L1缺乏症对胰岛功能的影响。将PDL1基因缺陷小鼠和野生型(WT)小鼠(C57BL/6J)分离的胰岛植入链脲佐菌素(STZ)诱导的糖尿病BALB/c小鼠肾被膜下。监测移植后血糖水平和移植物存活时间。此外，我们还分析了来自受体的残留胰岛、浸润性免疫细胞和同种异体反应细胞。结果胰岛内PD-L1缺乏不影响胰岛功能。然而，胰岛PD-L1缺乏增加了同种异体移植排斥反应，并与炎性细胞浸润和受体T细胞同种反应性增加有关。结论首次报道PD-L1缺乏可加速同种异体胰岛移植排斥反应并调节受体的同种免疫反应。
Background Islet transplantation may potentially cure type 1 diabetes mellitus (T1DM). However, immune rejection, especially that induced by the alloreactive T-cell response, remains a restraining factor for the long-term survival of grafted islets. Programmed death ligand-1 (PD-L1) is a negative costimulatory molecule. PD-L1 deficiency within the donor heart accelerates allograft rejection. Here, we investigate whether PD-L1 deficiency in donor islets reduces allograft survival time. Methods Glucose Stimulation Assays were performed to evaluate whether PD-L1 deficiency has detrimental effects on islet function. Islets isolated from PDL1-deficient mice or wild- type (WT) mice (C57BL/6j) were implanted beneath the renal capsule of streptozotocin (STZ)-induced diabetic BALB/c mice. Blood glucose levels and graft survival time after transplantation were monitored. Moreover, we analyzed the residual islets, infiltrating immune cells and alloreactive cells from the recipients. Results PD-L1 deficiency within islets does not affect islet function. However, islet PD-L1 deficiency increased allograft rejection and was associated with enhanced inflammatory cell infiltration and recipient T-cell alloreactivity. Conclusions This is the first report to demonstrate that PD-L1 deficiency accelerated islet allograft rejection and regulated recipient alloimmune responses.