Functional Expression of B7H1 and B7DC on Retinal Pigment Epithelial Cells

Abstract

Purpose: : The interaction of programmed death–1 (PD–1) expressed on T cells with its ligands B7H1 (PDL1) and B7DC (PDL2) is known to be a mechanism of T cell inhibition. In the present study, we examined whether human or murine retinal pigment epithelial cells (RPE) express B7H1 and B7DC, and if so, whether these molecules on RPE cells play an inhibitory role via interaction with T cells.

Methods: : The transcriptional levels and surface expression of B7H1 and B7DC on human RPE cell line (ARPE–19), RPE cells freshly isolated from healthy controls, and murine RPE cells were studied by reverse transcription–polymerase chain reaction (RT–PCR) and flow cytometry. In addition, T cells from healthy controls were cultured with ARPE–19 for 72 hours in the presence or absence of monoclonal antibody (mAb) to B7H1 or B7DC, and T cell proliferation responses were measured.

Results: : Messenger and cell surface protein expressions of both B7H1 and B7DC were demonstrated on ARPE–19 or freshly isolated human RPE cells, and these expressions were predominantly upregulated by treatment with interferon–γ (IFN–γ). In murine RPE cells, B7H1 expression was detected only when stimulated with IFN–γ. Proliferative responses of T cells co–cultured with ARPE–19 were dramatically enhanced in the presence of anti B7H1 mAb or anti B7DC mAb.

Conclusions: : These data suggest that B7H1 and B7DC expressed on RPE cells play an immunosuppressive role in ocular inflammation, which may contribute to immune privilege in the posterior segment of the eye.

Keywords: retinal pigment epithelium • immunomodulation/immunoregulation • cell membrane/membrane specializations