Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells.
OBJECTIVE
To evaluate the expression and regulation of a novel B7-like protein, PD-L1, the ligand for the immunoinhibitory receptor PD-1 expressed on activated T-cells, on microvascular endothelial cells (ECs)


METHODS
PD-L1 expression on ECs in vitro and in vivo was quantified by using a dual radiolabeled antibody technique after treatment with interferons (IFN) and IL-12, respectively. Changes in the level of PD-L1 mRNA were determined by using RT-PCR.


RESULTS
PD-L1 was observed to be present on ECs under basal conditions. Treatment of ECs with IFN-alpha, -beta and -gamma, but not LPS, was observed to induce elevations in the mRNA and surface expression of PD-L1 on ECs. By using a dual radiolabeled monoclonal antibody (mAb) technique, PD-L1 expression in various tissues of control and IL-12 challenged wild-type and IFN-gamma-deficient mice was measured. A significant increase in PD-L1 expression was observed in tissues at 24 hours after IL-12-challenge, with peak levels of PD-L1 occurring 72 hours after IL-12 challenge. IL-12 was not effective at inducing PD-L1 expression in tissues of IFN-gamma-deficient mice.


CONCLUSIONS
These data show the expression of a novel B7-like molecule on murine ECs that is mediated by IFN-alpha, -beta, and -gamma, and suggest a potential pathway by which ECs may modulate T-cell function.
Eppihimer
Michael J
MJ
Discovery Research: Respiratory Diseases, Wyeth/Genetics Institute, Andover, MA 01810, USA. meppihimer@genetics.com
Gunn
Jason
J
Freeman
Gordon J
GJ
Greenfield
Edward A
EA
Chernova
Tetyana
T
Erickson
Jamie
J
Leonard
John P
JP
D000818:Animals; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology; D018664:Interleukin-12 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008833:Microcirculation / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000276:immunology
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C498919:Cd274 protein, mouse; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018664:Interleukin-12; D007371:Interferon-gamma