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Endothelial expression of PD‐L1 and PD‐L2 down‐regulates CD8 + T cell activation and cytolysis
Author(s) -
Rodig Nancy,
Ryan Timothy,
Allen Jessica A.,
Pang Hong,
Grabie Nir,
Chernova Tatyana,
Greenfield Edward A.,
Liang Spencer C.,
Sharpe Arlene H.,
Lichtman Andrew H.,
Freeman Gordon J.
Publication year - 2003
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.200324270
Subject(s) - biology , cytotoxic t cell , microbiology and biotechnology , endothelial stem cell , cd8 , t cell , interleukin 21 , cytolysis , antigen presenting cell , immune system , immunology , in vitro , biochemistry
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 + 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.