Expression and Regulation of the PD-L1 Immunoinhibitory Molecule on Microvascular Endothelial Cells

Abstract

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-α, -β and -γ, 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-γdeficient 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-γ-deficient mice.Conclusions-These data show the expression of a novel B7-like molecule on murine ECs that is mediated by IFN-α, -β, and -γ, and suggest a potential pathway by which ECs may modulate Tcell function.