@article {542621,
	title = {Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis.},
	journal = {Eur J Immunol},
	volume = {33},
	number = {11},
	year = {2003},
	month = {2003 Nov},
	pages = {3117-26},
	abstract = {Interactions between CD8+ T cells and endothelial cells are important in both protective and pathologic immune responses. Endothelial cells regulate the recruitment of CD8+ T cells into tissues, and the activation of CD8+ T cells by antigen presentation and costimulatory signals. PD-L1 and PD-L2 are recently described B7-family molecules which bind to PD-1 on activated lymphocytes and down-regulate T cell activation. We found that PD-L1 is expressed on interferon-gamma stimulated cultured human and mouse endothelial cells, while PD-L2 was found on stimulated human but not mouse endothelial cells. Expression was further up-regulated by TNF-alpha. Antibody blockade of endothelial cell PD-L1 and PD-L2 enhanced endothelial cell costimulation of PHA-activated human CD8+ T cells. Antibody blockade of mouse endothelial cell PD-L1 enhanced both IFN-gamma secretion and cytolytic activity of CD8+ T cells in response to endothelial cell antigen presentation. These results show that IFN-gamma activated endothelial cells can inhibit T cell activation via expression of the immunoinhibitory PD-L1 and PD-L2 molecules. Endothelial expression of PD-ligands would allow activation and extravasation of T cells without excessive vessel damage. Our findings highlight a potentially important pathway by which endothelial cells down-regulate CD8+ T cell-mediated immune responses.},
	keywords = {Animals, Antigen-Presenting Cells, Antigens, CD, Antigens, CD274, Antigens, CD80, Blood Proteins, CD8-Positive T-Lymphocytes, Endothelium, Vascular, Humans, Intercellular Signaling Peptides and Proteins, Membrane Glycoproteins, Mice, Peptides, Programmed Cell Death 1 Ligand 2 Protein},
	issn = {0014-2980},
	doi = {10.1002/eji.200324270},
	author = {Rodig, Nancy and Ryan, Timothy and Allen, Jessica A and Pang, Hong and Grabie, Nir and Chernova, Tatyana and Greenfield, Edward A and Liang, Spencer C and Sharpe, Arlene H and Lichtman, Andrew H and Freeman, Gordon J}
}
