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 aft or 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.