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Sunao Sugita, Masayo Takahashi; Retinal pigment epithelial cells (RPE) induced from induced pluripotent stem (iPS) cells inhibit activation of T cells in vitro. Invest. Ophthalmol. Vis. Sci. 2013;54(15):145.
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To determine whether human retinal pigment epithelial cells (RPE) from induced pluripotent stem (iPS) cells can inhibit T-cell activation in vitro.
Cultured iPS-derived RPE cells (iPS-RPE) were established from fresh skin tissues (skin fibroblasts) obtained from healthy donors after informed consent was obtained. Target activated T cells were established from autogeneic or allogeneic T cells (CD4 or CD8) from peripheral blood mononuclear cells. As another targets, T cell clones of patients with active uveitis were established from ocular fluid by the limiting dilution. T-cell activation was assessed for proliferation by BrdU incorporation or IFN-γ production by the target T cells. Expression of TGFβ and costimulatory molecules on iPS-RPE was evaluated with flow cytometry, immunohistochemistry, and quantitative RT-PCR.
Cultured iPS-RPE cells significantly inhibited T cell proliferation and IFN-γ production by T cells when the target T cells were stimulated with anti-human CD3/CD28 antibodies for 72 hr. iPS-RPE cells significantly suppressed the activation of intraocular T cells from patients with active uveitis. The iPS-RPE cells constitutively expressed TGFβ and negative costimulatory molecules such as B7-H1 (PD-L1). In addition, TGFβ and/or B7-H1-siRNA-treated iPS-RPE cells failed to inhibit the activation of T cells.
Cultured human iPS-derived RPE cells fully suppress T cell activation in vitro. Transplantation of iPS-RPE cells into the eye may be a therapy for ocular diseases. They might reduce T-cell mediated immune rejection.
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