Immunological Properties of Human Embryonic Stem Cell-Derived Retinal Pigment Epithelial Cells

Abstract

Summary: Age-related macular degeneration is caused by dysfunction and loss of retinal pigment epithelium (RPE) cells, and their transplantation may rescue visual functions and delay disease progression. Human embryonic stem cells (hESCs) may be an unlimited source of RPE cells for allotransplantation. We analyzed the immunomodulatory properties of hESC-derived RPE (hESC-RPE) cells, and showed that they inhibited T cell responses. Co-culture experiments showed that RPE cells inhibited interfon-γ secretion and proliferation of activated T cells. Furthermore, hESC-RPE cells enhanced T cell apoptosis and secretion of the anti-inflammatory cytokine interleukin-10 (IL-10). In addition, RPE cells altered the expression of T cell activation markers, CD69 and CD25. RPE cells transplanted into RCS rats without immunosuppression survived, provided retinal rescue, and enhanced IL-10 blood levels. Our data suggest that hESC-RPE cells have immunosuppressive properties. Further studies will determine if these properties are sufficient to alleviate the need for immunosuppression therapy after their clinical allotransplantation. : In this article, Reubinoff and colleagues describe the immunomodulatory properties of hESC-RPE cells. They show that the RPE cells inhibit IFN-γ secretion and proliferation of T cells and enhance T cells apoptosis and secretion of IL-10. In the absence of immunosuppression therapy, RPE cells survive, provide retinal rescue, and enhance IL-10 blood levels in a rat model of retinal degeneration. These findings are relevant to designing immunosuppressive regimens for RPE cell allotransplantation therapies. Keywords: retinal pigment epithelium, human embryonic stem cells, immunomodulation, immune-privilege