Regulation of PD-1, PD-L1, and PD-L2 Expression During Normal and Autoimmune Responses

Eur J Immunol. 2003 Oct;33(10):2706-16. doi: 10.1002/eji.200324228.

Abstract

Newer members of the B7-CD28 superfamily include the receptor PD-1 and its two ligands, PD-L1 and PD-L2. Here, we characterize the expression of PD-1, PD-L1, and PD-L2 in tissues of naive miceand in target organs from two models of autoimmunity, the pancreas from non-obese diabetic (NOD) mice and brain from mice with experimental autoimmune encephalomyelitis (EAE). In naive mice, proteiexpression of PD-1, PD-L1, and PD-L2 was detected in the thymus, while PD-1 and PD-L1 were detected in the spleen. PD-L1, but not PD-L2, was also detected at low levels on cardiac endothelium, pancreatic islets, and syncyciotrophoblasts in the placenta. In pre-diabetic NOD mice, PD-1 and PD-L1 were expressed on infiltrating cells in the pancreatic islets. Furthermore, PD-L1 was markedly up-regulated on islet cells. In brains from mice with EAE, PD-1, PD-L1, and PD-L2 were expressed on infiltrating inflammatory cells, and PD-L1 was up-regulated on endothelium within EAE brain. The distinct expression patterns of PD-L1 and PD-L2 led us to compare their transcriptional regulation in STAT4(-/-), STAT6(-/-), or NF-kappaB p50(-/-)p65(+/-) dendritic cells (DC).PD-L2, but not PD-L1, expression was dramatically reduced in p50(-/-)p65(+/-) DC. Thus, PD-L1 and PD-L2 exhibit distinct expression patterns and are differentially regulated on the transcriptional level.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Surface / analysis*
  • Apoptosis Regulatory Proteins
  • Autoimmune Diseases / metabolism*
  • B7-1 Antigen*
  • B7-H1 Antigen
  • Blood Proteins / analysis*
  • CHO Cells
  • Cricetinae
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Germinal Center / chemistry
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • NF-kappa B / physiology
  • Peptides / analysis*
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • STAT6 Transcription Factor
  • Spleen / chemistry
  • Thymus Gland / chemistry
  • Trans-Activators / physiology
  • Transfection
  • Up-Regulation

Substances

  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • Cd274 protein, mouse
  • Membrane Glycoproteins
  • NF-kappa B
  • Pdcd1 protein, mouse
  • Pdcd1lg2 protein, mouse
  • Peptides
  • Programmed Cell Death 1 Ligand 2 Protein
  • Programmed Cell Death 1 Receptor
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Trans-Activators