The last two authors share senior authorship.
Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis
Article first published online: 13 OCT 2003
Copyright © 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
European Journal of Immunology
Volume 33, Issue 11, pages 3117–3126, November 2003
How to Cite
Rodig, N., Ryan, T., Allen, Jessica A., Pang, H., Grabie, N., Chernova, T., Greenfield, Edward A., Liang, S. C., Sharpe, Arlene H., Lichtman, Andrew H. and Freeman, Gordon J. (2003), Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis. Eur. J. Immunol., 33: 3117–3126. doi: 10.1002/eji.200324270
- Issue published online: 13 OCT 2003
- Article first published online: 13 OCT 2003
- Manuscript Accepted: 8 SEP 2003
- Manuscript Revised: 11 AUG 2003
- Manuscript Received: 18 JUN 2003
- T lymphocytes;
- Endothelial cells;
Interactions between CD8+ T cells and endothelial cells are important in both protective and pathologic immune responses. Endothelial cells regulate the recruitment of CD8+ Tcells 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-γ 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-α. 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-γ secretion and cytolytic activity of CD8+ T cells in response to endothelial cellantigen presentation. These results show that IFN-γ 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.