期刊
CLINICAL IMMUNOLOGY
卷 115, 期 2, 页码 184-191出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2005.01.005
关键词
renal tubular epithelial cells; PD-L1; T cells; cytokine
类别
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.
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