PD-L1 is expressed by human renal tubular epithelial cells and suppresses T cell cytokine synthesis
PD-L1 is expressed by human renal tubular epithelial cells and suppresses T cell cytokine synthesis
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DOI：
10.1016/j.clim.2005.01.005
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发表时间：
2005-05-01
影响因子：
8.6
通讯作者：
Gao, W
中科院分区：
文献类型：
--
作者：
Ding, HL;Wu, XF;Gao, W
T细胞的激活既受刺激信号的影响，也受抑制信号的影响。表达NIHC-II类的肾小管上皮细胞(TEC)可作为T细胞的APC。为了研究抑制性配体对TEC介导的T细胞活化的影响，我们检测了人TEC细胞系HK-2细胞以及正常和病变肾脏标本中程序性死亡配体-1(PD-L1)的表达。RT-PCR、FACS和免疫细胞化学显示PD-L1在HK-2细胞上有结构性表达，并被干扰素-γ显著上调。原位杂交和免疫组织化学染色显示PD-L1在正常肾脏近端小管上呈低表达，而在IV型狼疮性肾炎肾组织中高表达。在体外，用抗PD-L1抗体预处理干扰素-γ刺激的HK-2细胞可显著增加共培养的有丝分裂原激活的Jurkat或人外周血T细胞分泌IL-2。以上结果提示，PD-L1：PD-1途径对TEC诱导的T细胞活化具有负性调节作用，可能在TEC介导的免疫激活和肾脏免疫病理过程中起抑制作用。(C)2005 Elsevier Inc.保留所有权利。
T cell activation is affected by both stimulatory and inhibitory co-signaling. NIHC class II-expressing renal tubular epithelial cells (TEC) can function as APC for T cells. To study the influence of inhibitory ligands oil TEC-mediated T cell activation, we examined the expression of programmed death ligand-1 (PD-L1) on human TEC line HK-2 cells, as well as in normal and diseased kidney samples. RT-PCR, FACS, and immunocytochemistry showed that PD-L1 is constitutively expressed on HK-2 cells, and is dramatically Upregulated by IFN-gamma. In situ hybridization and immunohistochemical staining revealed constitutive low expression of PD-L1 on proximal tubules at both mRNA and protein levels in normal kidneys, but much higher expression in kidneys with type IV lupus nephritis. In vitro, pretreatment of IFN-gamma-stimulated HK-2 cells with anti-PD-L1 significantly enhanced IL-2 secretion from cocultured, mitogen-activated Jurkat or human peripheral blood T cells. These results suggest that the PD-L1:PD-1 pathway negatively regulates T cell activation by TEC, and may play an inhibitory role in TEC-mediated immune activation and immunopathology in the kidney. (c) 2005 Elsevier Inc. All rights reserved.