Suppressed T-cell activation by IFN-γ-induced expression of PD-L1 on renal tubular epithelial cells
Suppressed T-cell activation by IFN-γ-induced expression of PD-L1 on renal tubular epithelial cells
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DOI：
10.1093/ndt/gfh423
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发表时间：
2004-11-01
影响因子：
6.1
通讯作者：
Wüthrich, RP
中科院分区：
文献类型：
--
作者：
Schoop, R;Wahl, P;Wüthrich, RP
背景资料。T细胞分子PD-1(程序性死亡-1)与其配体PD-L1和PD-L2的相互作用代表了已知的T细胞抑制机制。PD-1与CD28同源，PD-1配体与共刺激分子B7家族同源。我们用流式细胞仪和逆转录聚合酶链式反应研究了小鼠肾小管上皮细胞(TEC)上PD-L1和PD-L2的表面表达和转录水平。Western印迹分析证实PD-L1蛋白的表达。我们还检测了PD-L1和PD-1在抗原提呈中的功能作用。此外，我们还对具有排斥反应的小鼠肾移植进行了PD-1配体的表达染色。我们发现PD-L1而不是PD-L2在未受刺激的TEC上有微弱的表达。在干扰素-γ刺激下，PD-L1的表达呈剂量依赖性上调。在抗原提呈试验中用单抗阻断PD-L1/PD-1通路，发现该配体系统在Th1和Th2细胞激活中具有抑制作用。在有排斥反应的小鼠肾移植中，近端和远端小管对PD-L1的耐受性很强，而正常肾脏和同基因小鼠移植肾的染色没有显示PD-L1的表达。结论：PD-L2在正常或排斥小鼠肾脏中未见表达。这些数据表明，PD-L1是一种可诱导的肾小管上皮细胞抗原，对干扰素-γ刺激的TEC诱导的T细胞反应具有负性调节作用。我们推测PD-I/PD-Li通路可能在免疫介导的肾小管间质损伤中起保护作用。
Background. The interaction of the T-cell molecule PD-1 (programmed death-1) with its ligands PD-L1 and PD-L2 represents a known mechanism of T-cell inhibition. PD-1 is homologous to CD28 while the PD-1 ligands share homology with the B7 family of co-stimulatory molecules.Methods. We have studied surface expression and transcript levels of PD-L1 and PD-L2 on murine renal tubular epithelial cells (TEC) by flow cytometric analysis and reverse transcription-polymerase chain reaction. Western blot analysis was used to confirm protein expression of PD-L1. We also tested the functional role of PD-L1 and PD-1 in antigen presentation. Furthermore, we stained mouse kidney transplants with rejection for the expression of the PD-1 ligands.Results. We found that PD-L1 but not PD-L2 was weakly expressed on unstimulated TEC. Upon stimulation with IFN-gamma, a dose-dependent Upregulation of PD-L1 expression was observed. Blockade of the PD-L1/PD-1 pathway with monoclonal antibodies in antigen presentation assays uncovered an inhibitory role of this ligand system in Th1 and Th2 cell activation. Stamina for PD-L1 was strong in proximal and distal tubules in mouse kidney transplants with rejection., whereas staining- of normal kidneys and syngenic mouse kidney transplants did not reveal PD-L1 expression. PD-L2 was not observed in normal or rejected mouse kidneys.Conclusions. These data demonstrate that PD-L1 is an inducible renal tubular epithelial antigen that negatively regulates T-cell responses elicited by IFN-gamma-stimulated TEC. We speculate that the PD-I/PD-LI pathway may play a role in protecting the epithelium from immune-mediated tubulointerstitial injury.