PD-L1 Expression on Human Ocular Cells and Its Possible Role in Regulating Immune-Mediated Ocular Inflammation

Abstract

PURPOSE: To assess the expression of PD-L1 and PD-L2 on human ocular cells and their potential to regulate ocular inflammation. METHODS: Five categories of human ocular cells were evaluated for PD-L1 and PD-L2 expression by RT-PCR and flow cytometry. Three normal eyes and an inflamed eye from a patient with sympathetic ophthalmia were examined by immunohistochemistry for in situ PD-L1 expression. The immunomodulatory functions of PD-L1 and PD-L2 were tested by coculturing untreated or IFN-gamma-pretreated ocular cells with activated human peripheral blood T cells for 48 hours and assessing T-cell production of IFN-gamma, TNF-alpha, IL-4, and IL-5 by ELISA and T-cell apoptosis by flow cytometry. RESULTS: PD-L1 protein was expressed constitutively in 4 of 5 human ocular cell lines, and its expression was significantly upregulated after stimulation by IFN-gamma. Moreover, in situ expression of PD-L1 in inflamed ocular tissues was remarkably upregulated compared with normal eyes. Although PD-L2 expression was detectable by flow cytometry on 3 of 5 ocular cell lines, immunohistochemical staining did not show expression of PD-L2 on either normal or inflamed ocular tissues. IFN-gamma, TNF-alpha, and IL-5 production by activated T cells cocultured with ocular cells was significantly enhanced in the presence of anti-PD-L1 blocking antibody. However, ocular cell-expressed PD-L1 and PD-L2 did not induce T-cell apoptosis. CONCLUSIONS: PD-L1 expressed on human ocular cells has a presumptive role in controlling ocular inflammation by inhibiting the production of proinflammatory cytokines and a Th2 cytokine by activated T cells. This may represent an important mechanism for maintaining immune privilege in the eye.