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S. Horie, S. Sugita, Y. Futagami, H. Keino, J.W. Streilein, M. Mochizuki; FOXP3+ CD25+ T Cells Induced by Ocular Pigment Epihelium Display Regulatory Phenotype and Aquire Regulatory Functions . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5137.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate whether T cells exposed to ocular pigment epithelial cells (PE) express CD25 and Foxp3, and the CD25+ PE–T cells display regulatory functions in vitro.
Primary cultured PE cells (iris PE or retinal PE) were established from normal C57BL/6 mice. T cells were co–cultured with PE, x–irradiated, and used as regulators (PE Tregs). Target bystander T cells were established from normal splenic T cells with anti–CD3 antibodies. T–cell activation was assessed for proliferation by [3H]–thymidine incorporation. The expression of CD25, GITR (glucocorticoid–induced TNF receptor family related gene), and CD103 on PE Tregs was evaluated by flow cytometry. T cells from CD25 deficient donors or CD25 depleted population were used to abolish regulatory function. The expression of Foxp3 transcripts on CD25+ PE Tregs was evaluated by semi–quantitative RT–PCR.
Cultured iris PE and retinal PE converted naïve T cells to CD25+ Tregs that suppressed the activation of bystander T cells. These CD25+ PE Tregs expressed GITR and CD103 constitutively. Similar to CD25+ PE Tregs, CD25 negative PE Tregs suppressed the activation of bystander T cells. T cells depleted of CD25+ cells or T cells disrupted for CD25 molecules prior to in vitro stimulation by PE cells still differentiated into Tregs. The ocular PE cells converted in CD25+ Tregs that expressed Foxp3 transcripts through TGF–b TGF–b receptor interactions. In addition, membrane–bound TGF–b+ CD25+ PE T cells, that acquired regulatory functions, expressed transcripts for many immunomodulatory molecules and Foxp3 transcripts.
One subset of Tregs of ocular pigment epithelial cells arises from CD25 negative precursors, and the induction of T cell–suppression does not require the presence of natural (conventional) CD25 Tregs.
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