The role of indoleamine 2,3-dioxygenase in retinal pigment epithelial cell-mediated immune modulation.
OBJECTIVE
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 (1-MT) into the culture medium successfully reversed RPE immunosuppression.


CONCLUSIONS
The expression of IDO may in part explain RPE-mediated immune suppression effects.
Park
Choul Yong
CY
Department of Ophthalmology, Dongguk University, School of Medicine, Koyang, South Korea.
Yang
Seung-Ha
SH
Chuck
Roy S
RS
Gehlbach
Peter L
PL
Park
Chung-Gyu
CG
D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology; D002478:Cells, Cultured; D006801:Humans; D007108:Immune Tolerance; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D007959:Lymphocyte Culture Test, Mixed; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D055213:Retinal Pigment Epithelium / Q000201:enzymology / Q000276:immunology*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000276:immunology
D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007371:Interferon-gamma; D014364:Tryptophan; C525396:1-methyltryptophan