The role of indoleamine 2,3-dioxygenase in retinal pigment epithelial cell-mediated immune modulation

Ocul Immunol Inflamm. 2010 Jan;18(1):24-31. doi: 10.3109/09273940903326203.

Abstract

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 (1-MT) into the culture medium successfully reversed RPE immunosuppression.

Conclusions: The expression of IDO may in part explain RPE-mediated immune suppression effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / immunology
  • B7-2 Antigen / immunology
  • Cells, Cultured
  • Humans
  • Immune Tolerance
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / immunology*
  • Interferon-gamma / immunology
  • Lymphocyte Culture Test, Mixed
  • Major Histocompatibility Complex / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred CBA
  • Retinal Pigment Epithelium / enzymology
  • Retinal Pigment Epithelium / immunology*
  • Tryptophan / analogs & derivatives
  • Tryptophan / immunology

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • CD86 protein, human
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Interferon-gamma
  • Tryptophan
  • 1-methyltryptophan