Human PD-L1-overexpressing porcine vascular endothelial cells induce functionally suppressive human CD4+CD25hiFoxp3+ Treg cells
Human PD-L1-overexpressing porcine vascular endothelial cells induce functionally suppressive human CD4+CD25hiFoxp3+ Treg cells
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DOI：
10.1189/jlb.1210691
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发表时间：
2011-07-01
影响因子：
5.5
通讯作者：
Chou, Kuang-Yen
中科院分区：
文献类型：
--
作者：
Ding, Qing;Lu, Liming;Chou, Kuang-Yen
在异种移植模型中，猪血管内皮细胞直接激活hCD4(+)T细胞导致T细胞的强劲增殖。为了探讨其可能的机制，我们用人抗猪MLEC培养法研究了跨物种细胞间的相互作用、hCD4(+)T细胞的增殖和人类细胞因子的诱导。我们报道，PIEC呈递异种抗原可以扩大hCD4(+)Foxp3(+)Tregs和hCD4(+)Foxp3(-)Teffs，这一过程依赖于猪MHC-II抗原的表达。稳定地将HPD-L1基因导入PIEC可抑制T细胞的增殖，但不影响T细胞的增殖。令人惊讶的是，PIEChPD-L1显著增强了hCD4(+)T细胞产生IL-10的能力。值得注意的是，HPD-L1诱导的Treg具有较高的抑制能力，部分通过IL-10和CD73介导抑制功能。本研究为利用高表达HPD-L1的猪血管内皮细胞作为治疗异种移植耐受的新方法提供了可能性，也支持了使用HPD-L1转基因猪作为异种移植供体的可能性。J.Leukoc。比奥尔。90：77-86；2011。
In xenotransplantation models, direct activation of hCD4(+) T cells by porcine VECs leads to a robust proliferation of T cells. To investigate the underlying mechanisms, human antiporcine MLEC culture was used to investigate cross-species cell interactions, proliferation of hCD4(+) T cells, and induction of human cytokines. We report that xenoantigen presentation by PIEC expands hCD4(+) Foxp3(+) Tregs and hCD4(+) Foxp3(-) Teffs, and this process is dependent on porcine MHC-II antigen expression. Stable transfection of hPD-L1 into PIEC inhibits Teff proliferation, but Treg proliferation is not affected. Surprisingly, IL-10 production by hCD4(+) T cells is augmented significantly by PIEChPD-L1. Notably, hPD-L1-induced Tregs have higher suppressive potency and mediate suppressive function partially through IL-10 and CD73. This study opens the possibility of using hPD-L1-overexpressing porcine VECs as a novel therapeutic to allow tolerance of xenotransplants and also supports the possibility of using hPD-L1 transgenic pigs as xenotransplant donors. J. Leukoc. Biol. 90: 77-86; 2011.