Capacity of Retinal Ganglion Cells Derived from Human Induced Pluripotent Stem Cells to Suppress T-Cells

Abstract

Retinal ganglion cells (RGCs) are impaired in patients such as those with glaucoma and optic neuritis, resulting in permanent vision loss. To restore visual function, development of RGC transplantation therapy is now underway. Induced pluripotent stem cells (iPSCs) are an important source of RGCs for human allogeneic transplantation. We therefore analyzed the immunological characteristics of iPSC-derived RGCs (iPSC-RGCs) to evaluate the possibility of rejection after RGC transplantation. We first assessed the expression of human leukocyte antigen (HLA) molecules on iPSC-RGCs using immunostaining, and then evaluated the effects of iPSC-RGCs to activate lymphocytes using the mixed lymphocyte reaction (MLR) and iPSC-RGC co-cultures. We observed low expression of HLA class I and no expression of HLA class II molecules on iPSC-RGCs. We also found that iPSC-RGCs strongly suppressed various inflammatory immune cells including activated T-cells in the MLR assay and that transforming growth factor-β2 produced by iPSC-RGCs played a critical role in suppression of inflammatory cells in vitro. Our data suggest that iPSC-RGCs have low immunogenicity, and immunosuppressive capacity on lymphocytes. Our study will contribute to predicting immune attacks after RGC transplantation.

Low Immunogenicity and Immunosuppressive Properties of Human ESC- and iPSC-Derived Retinas

“…(2) RPE cells and iris/ciliary body epithelial cells have immunosuppressive properties due to secretion of soluble factors, such as transforming growth factor β (TGF-β), that inhibit activation of immune cells ( Sugita, 2009 ; Sugita et al., 2006 ). Recently, we showed that retinal ganglion cells can suppress bystander T cells in vitro and produce TGF-β like RPE cells ( Edo et al., 2020 ).…”

SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids

“…TGFβ signaling has an important role in maintaining the immune-privileged status of the eye (Masli and Vega, 2011; Zhou and Caspi, 2010). For example, both RPE cells and RGCs suppress the activation of T cells via the secretion of TGFβ molecules (Edo et al, 2020; Sugita et al, 2011). Unlike most of the CNS, the choroid plexus is not an immune-privileged structure (Galea et al, 2007).…”

SARS-CoV-2 infects and replicates in photoreceptor and retinal ganglion cells of human retinal organoids

“…TGF-b signaling plays an important role in maintaining the immune-privileged status of the eye (Masli and Vega, 2011;Zhou and Caspi, 2010). For example, both RPE cells and RGCs suppress the activation of T cells via the secretion of TGF-b molecules (Edo et al, 2020;Sugita et al, 2011). Unlike most of the CNS, the choroid plexus is not an immune-privileged structure (Galea et al, 2007).…”