The Role of Indoleamine 2,3-Dioxygenase in Retinal Pigment Epithelial Cell-mediated Immune Modulation

Purpose: To evaluate the role of indoleamine dioxygenase (IDO) in human retinal pigment epithelial cell (RPE)-mediated immune modulation. Methods: The immunosuppression of cultured human RPEs (ARPE-19 cells) was assayed using the mixed lymphocyte reaction (MLR) harvested from CBA/J and BALB/c mice. The expression of critical immune modulatory molecules, such as class II major histocompatibility complex (MHC) molecules, co-stimulatory molecules (B7-1 and B7-2), and indoleamine dioxygenase (IDO), was examined by reverse transcriptase polymerase chain reaction, flow cytometry, and immunofluorescence staining with and without IFN-gamma stimulation. Results: RPEs expressed IDO and class II MHC molecules under IFN-gamma stimulation. However, B7-1 and B7-2 were not expressed. RPE significantly suppressed MLR in the absence of IFN-gamma prestimulation. This phenomenon was enhanced by IFN-gamma stimulation. The addition of 1-methyl tryptophan l into the culture medium successfully reversed RPE immunosuppression. Conclusions: The expression of IDO may in part explain RPE-mediated immune suppression effects.