Transplantation of NIT-1 Cells Expressing pD-L1 for Treatment of Streptozotocin-Induced Diabetes
Transplantation of NIT-1 Cells Expressing pD-L1 for Treatment of Streptozotocin-Induced Diabetes
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DOI：
10.1097/tp.0b013e31818c6e64
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发表时间：
2008-12
期刊：
影响因子：
6.2
通讯作者：
Xue Wen;Hui-fen Zhu;Li Li-Li;Yan Li;Min Wang;Jing Liu;Daofeng Yang;Wenjun Liao;G. Shen
中科院分区：
文献类型：
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作者：
Xue Wen;Hui-fen Zhu;Li Li-Li;Yan Li;Min Wang;Jing Liu;Daofeng Yang;Wenjun Liao;G. Shen
背景。程序性死亡-1配体-1（PD-L1、CD274、B7-H1）已被确定为免疫抑制性受体程序性死亡-1的配体，并已被证明在免疫反应和外周耐受的调节中发挥作用。在这项研究中，我们测试了从转基因 NDD/Lt 小鼠 (NIT) 建立的 PD-L1 转染的胰腺 β 细胞系对同种异体反应和链脲佐菌素诱导的糖尿病的影响。方法。采用低剂量链脲佐菌素对Balb/C小鼠建立糖尿病模型。建立了PD-L1转染的NIT细胞系，即NIT-PD-L1。通过腹腔注射将NIT-1、空载体转染的NIT-1或NIT-PD-L1细胞分别移植到糖尿病小鼠体内。通过羧基荧光素琥珀酰亚胺酯或AnnexinV-Cy5标记和增殖指数（PI）检测脾淋巴细胞的增殖和凋亡。通过酶联免疫吸附测定和流式细胞术分析测定细胞因子。结果。与对照组相比，NIT-1 细胞上 PD-L1 的过度表达可显着延长糖尿病小鼠同种异体移植物的存活率。在混合细胞反应中，移植 NIT-PD-L1 的糖尿病小鼠的脾淋巴细胞与丝裂霉素 C 处理的 NIT-PD-L1 共培养，表现出最低的增殖反应，但出现严重的凋亡。此外，NIT-PD-L1 抑制了这些淋巴细胞在体外和体内产生的干扰素，但上调了白细胞介素 4 和 -10 的产生。结论。我们的数据表明，胰腺细胞上PD-L1的过度表达可以显着延长同种异体移植物的存活，并且与抑制淋巴细胞活化和增殖、诱导淋巴细胞凋亡有关。
Background. Programmed death-1 ligand-1 (PD-L1, CD274, B7-H1) has been identified as the ligand for the immunoinhibitory receptor programmed death-1 and has been demonstrated to play a role in the regulation of immune responses and peripheral tolerance. In this study, we tested the effect of PD-L1-transfected pancreatic beta-cell line established from a transgenic NDD/Lt mouse (NIT) on the alloresponse and streptozotocin-induced diabetes. Methods. The diabetes model was established by a low dose of streptozotocin in Balb/C mice. PD-L1 transfected NIT cell line was established, namely NIT-PD-L1. NIT-1, empty vector-transfected NIT-1, or NIT-PD-L1 cells were transplanted into diabetic mice by intraperitoneal injection, respectively. Proliferation and apoptosis of splenic lymphocytes were detected by labeling with carboxy fluoroscein succinimidyl ester or AnnexinV-Cy5 and proliferation index (PI). Cytokines were determined by enzyme-linked immunosorbent assay and flow cytometry analysis. Results. When compared with the controls, overexpression of PD-L1 on NIT-1 cells markedly prolonged allograft survival in diabetic mice. In mixed cells reaction, splenic lymphocytes from NIT-PD-L1-transplanted diabetic mice co-culture with mitomycin C-treated NIT-PD-L1 showed the lowest proliferative response but severe apoptosis. In addition, NIT-PD-L1 suppressed interferon- but up-regulated interleukin-4 and -10 productions by those lymphocytes in vitro and in vivo. Conclusion. Our data demonstrated that overexpression of PD-L1 on pancreatic cells significantly can prolong allograft survival, and it is associated with inhibition of lymphocytes activation and proliferation, induction of lymphocytes apoptosis.