Purchase this article with an account.
J.Y. Niederkorn, S. Wang, D. Dace; Expression of indoleamine dioxygenase (IDO) by uveal melanomas and ocular cells . Invest. Ophthalmol. Vis. Sci. 2004;45(13):591.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Purpose:Indoleamine 2,3–dioxygenase (IDO) catalyzes tryptophan degradation. T lymphocytes are extremely sensitive to tryptophan deprivation and undergo proliferation arrest when subjected to tryptophan shortage. IDO expression by the placenta is an important mechanism for maintaining immune privilege at the maternal/fetal interface and is believed to prevent immune rejection of allogeneic fetuses. The aim of this study was to determine if uveal melanoma cells and ocular cells express IDO and if IDO expression can be upregulated by a proinflammatory cytokine, interferon–gamma. Methods:Twelve human uveal melanoma cell lines were examined by flow cytometry for their expression of IDO. Paraffin–embedded human eye sections were examined by immunohistochemistry for in situ expression of IDO. Human uveal melanoma cells were examined by flow cytometry for IDO expression following incubation in recombinant human interferon–gamma. The capacity of human uveal melanoma cells to induce upregulation of IDO in human macrophages and a murine Langerhans cell line was tested by co–culturing these two cell populations in a transwell culture system in which either macrophages or Langerhans cells and melanoma cells were separated by a semi–permeable membrane. Macrophages and Langerhans cells were examined for IDO expression by flow cytometry and the mean fluorescence intensity was determined before and after co–culture with melanoma cells. Results:Eight of the 12 uveal melanoma cell lines expressed cytoplasmic IDO in >20% of the cells. Exposure to interferon–gamma resulted in a 0%, 75%, and 100% increase in cytoplasmic IDO expression in MEL270, OM431, and OCM3 melanoma cells respectively. Macrophages and Langerhans cells co–cultured with uveal melanoma cells for 48 hours displayed a >100% increase in cytoplasmic IDO expression. Immunohistochemical examination of human eyes revealed cytoplasmic IDO expression in the corneal epithelium, corneal endothelium, and retina. Conclusions:It has been repeatedly demonstrated that IDO profoundly inhibits T cell proliferation and viability. The expression of IDO by ocular cells and uveal melanoma cells raises the possibility that this enzyme may augment ocular immune privilege and also protect uveal melanoma cells from tumor–infiltrating T cells.
This PDF is available to Subscribers Only