(Journal Article): Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis.
 
Rodig N, Ryan T, Allen JA, Pang H, Grabie N, Chernova T, Greenfield EA, Liang SC, Sharpe AH, Lichtman AH, Freeman GJ (The Immunology Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.)
 
IN: Eur J Immunol 2003; 33(11):3117-3126
Impact Factor(s) of Eur J Immunol: 5.005 (2004), 4.536 (2003), 4.832 (2002), 4.99 (2001)

Fulltext:    HTML  PDF

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.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Yadav D, Sarvetnik N. Costimulation and Pancreatic Autoimmunity: The PD-1/PD-L Conundrum. Rev Diabetic Stud 2006. 3: 6-10.
  » Diabetes OD » Development and Function of Pa... » Immune System » Activation and Inhibition » Costimulation » Programmed Death » Journal Article