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Y. Ke, G. Jiang, D. Sun, H. J. Kaplan, H. Shao; Conversion of Uveitogenic T Cells to Regulatory T Cells by PDL-1high Retinal Pigment Epithelium (RPE). Invest. Ophthalmol. Vis. Sci. 2010;51(13):820.
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To investigate the regulation of effector IRBP-specific T cells by RPE with high expression of PDL-1 (PDL-1high RPE).
The expression of PD-L1 on isolated RPE cells was examined after exposure to graded doses of IL-17, IFN-γ or the TLR3 ligand (Poly I: C) by flow cytometry. Proliferation, cytokine production, and suppression of interphotoreceptor binding protein (IRBP)-specific T cells were determined after co-culture with RPE cells expressing different levels of PDL-1.
RPE cells constitutively express a low level of PDL-1. The expression of PDL-1 is dramatically increased after exposure to IL-17, IFN-γ or Poly I:C in a dose dependent manner. After incubation with PDL-1high RPE cells, IRBP specific T cells markedly reduced their ability to proliferate and produce IL-17/IFN-γ after subsequent antigenic challenge. Adoptive transfer of these cells did not result in autoimmune uveitis. In contrast, they became regulatory T cells with the expression of FoxP3, CTLA-4 and IL-10, and inhibited the proliferation of IRBP-specific T cells in an antigen-specific manner. The suppressive activity of these T cells induced by exposure to PDL-1high RPE cells could be reversed by anti-PDL-1 antibodies.
IRBP-specific effector T cells can be converted to antigen-specific regulatory T cells following exposure to RPE with PDL-1 high expression. This regulatory role of RPE may be an important mechanism to suppress intraocular inflammation.
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