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Sunao Sugita, Hiroyuki Kamao, Yuko Iwasaki, Satoshi Okamoto, Tomoyo Hashiguchi, Kyoko Iseki, Naoko Hayashi, Michiko Mandai, Masayo Takahashi; Inhibition of T-Cell Activation by Retinal Pigment Epithelial Cells Derived From Induced Pluripotent Stem Cells. Invest. Ophthalmol. Vis. Sci. 2015;56(2):1051-1062. doi: 10.1167/iovs.14-15619.
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© ARVO (1962-2015); The Authors (2016-present)
The purpose of this study was to determine whether human retinal pigment epithelial (RPE) cells from induced pluripotent stem (iPS) cells could inhibit T-cell activation in vitro.
Cultured iPS-derived RPE (iPS-RPE) cells were established from fresh skin tissues or dental pulp cells obtained from healthy donors or a retinal patient after informed consent was obtained. To confirm expression of the specific markers on iPS and iPS-RPE cells, immunohistochemistry, quantitative RT-PCR (qRT-PCR), and flow cytometry were performed. Target T cells were obtained from peripheral blood mononuclear cells of healthy donors. Target T cells were assessed for proliferation by incorporation of bromodeoxyuridine or carboxyfluorescein succinimidyl ester for production of cytokines such as IFN-γ. Expression of TGFβ and other candidate molecules by iPS-RPE cells was evaluated with flow cytometry, ELISA, multiplex cytokine array, immunohistochemistry, and qRT-PCR.
The RPE cells we established from iPS cells had many characteristics of mature RPE cells but no characteristics of pluripotent stem cells. Cultured iPS-RPE cells inhibited cell proliferation and production of IFN-γ by activated CD4+ T cells. In some bystander T cells, iPS-derived RPE cells induced CD25+Foxp3+ regulatory T cells in vitro. Induced pluripotent stem-RPE cells constitutively expressed TGFβ and suppressed activation of T cells via soluble TGFβ, because TGFβ-downregulated iPS-RPE cells did not inhibit this T-cell activation.
Cultured iPS-derived retinal cells fully suppress T-cell activation. Transplantation of iPS-RPE cells into the eye might be a therapy for retinal disorders.
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