PD-L1 is expressed by human renal tubular epithelial cells and suppresses T cell cytokine synthesis

Clin Immunol. 2005 May;115(2):184-91. doi: 10.1016/j.clim.2005.01.005.


T cell activation is affected by both stimulatory and inhibitory co-signaling. MHC class II-expressing renal tubular epithelial cells (TEC) can function as APC for T cells. To study the influence of inhibitory ligands on 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.

MeSH terms

  • Antigens, CD
  • Antigens, Surface / genetics
  • Antigens, Surface / metabolism*
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen / genetics
  • B7-1 Antigen / metabolism*
  • B7-H1 Antigen
  • Cytokines / metabolism
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Kidney Tubules / cytology
  • Kidney Tubules / metabolism*
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / metabolism*
  • Peptides / genetics
  • Peptides / metabolism*
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger / metabolism
  • T-Lymphocytes / immunology*


  • Antigens, CD
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • CD274 protein, human
  • Cytokines
  • Interleukin-2
  • Membrane Glycoproteins
  • PDCD1 protein, human
  • Peptides
  • Programmed Cell Death 1 Receptor
  • RNA, Messenger
  • Interferon-gamma