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. 2003 Nov;33(11):3117-26.
doi: 10.1002/eji.200324270.

Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis

Nancy Rodig  1 , Timothy Ryan, Jessica A Allen, Hong Pang, Nir Grabie, Tatyana Chernova, Edward A Greenfield, Spencer C Liang, Arlene H Sharpe, Andrew H Lichtman, Gordon J Freeman
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Free article

Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis

Nancy Rodig et al. Eur J Immunol. 2003 Nov.
Free article

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.

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