Inhibition of T-Cell Activation by Retinal Pigment Epithelial Cells Derived From Induced Pluripotent Stem Cells

PURPOSE. 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. METHODS. 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-alpha. Expression of TGFb beta and other candidate molecules by iPS-RPE cells was evaluated with flow cytometry, ELISA, multiplex cytokine array, immunohistochemistry, and qRT-PCR. RESULTS. 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-alpha 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 TGF beta and suppressed activation of T cells via soluble TGF beta, because TGF beta-downregulated iPS-RPE cells did not inhibit this T-cell activation. CONCLUSIONS. 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.