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Y. Futagami, S. Sugita, S. Horie, J. Vega, K. Ishida, H. Aburatani, J.W. Streilein, M. Mochizuki; T Cell Suppression by Thrombospondin–1 on Pigment Epithelium (PE) and PE–Dependent Regulatory T Cells in the Eye . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5136.
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To examine whether ocular pigment epithelial cells (PE) promote generation of regulatory T cells (PE Tregs) by thrombospondin–1 (TSP–1).
Primary cultured PE (iris PE, ciliary body PE, and retinal PE) were established from normal C57BL/6 mice. T cells were co–cultured with PE, x–irradiated, and used as regulators. Target bystander T cells were established from normal splenic T cells with anti–CD3 antibodies. T–cell activation was assessed by [3H]–thymidine incorporation. The expression of TSP–1 on ocular PE and PE–exposed T cells was evaluated with oligonucleotide microarray, RT–PCR, immune staining, western blots and flow cytometry. Neutralizing anti–TSP–1 antibodies or T cells from TSP–1 null donors were used to abolish regulatory function.
Microarray for ocular PE demonstrated that PE expressed transcripts for immunoregulatory factors (TGFß, thrombospondins, macrophage migration inhibitory factor, CD59, IL–1 receptor antagonist and so on). Among the immunoregulatory factors, primary cultured PE constitutively expressed TSP–1 as well as TGFß. The PE cells produce TSP–1 which, in part through conversion of latent to active TGFß, generated PE Tregs. The regulatory T cell generation was amplified when T cells themselves express TSP–1. The ocular PE and PE Tregs suppressed activation of bystander T cells via surface TSP–1.
The ability of ocular PE and PE Tregs to suppress bystander T cells depends on their capacity to produce TSP–1 that is powerful mediators to promote active TGFß. Thus, intraocular TSP–1 produced by ocular parenchymal cells and the regulatory T cells is essential for immune regulation in the eye.
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