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

• Published in: International journal of molecular sciences 2020-10, Vol.21 (21), p.7831
• Main Authors: Edo, Ayaka, Sugita, Sunao, Futatsugi, Yoko, Sho, Junki, Onishi, Akishi, Kiuchi, Yoshiaki, Takahashi, Masayo
• Format: Article
• Language: English
• Subjects: Cell Differentiation; Coculture Techniques; Cytokines; Cytotoxicity; Evaluation; Glaucoma; Graft Rejection; Growth factors; Histocompatibility antigen HLA; HLA Antigens - genetics; HLA Antigens - immunology; HLA Antigens - metabolism; Humans; Immune system; Immune Tolerance; Immunogenicity; Immunology; Induced Pluripotent Stem Cells - cytology; Inflammation; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Lymphocytes; Lymphocytes T; Mixed leukocyte reaction; Morphology; Neuritis; Optic neuritis; Pluripotency; Recovery of function; Retina; Retinal ganglion cells; Retinal Ganglion Cells - cytology; Retinal Ganglion Cells - immunology; Retinal Ganglion Cells - transplantation; Stem cells; T-Lymphocytes - immunology; Transforming Growth Factor beta - metabolism; Transplantation; Visual perception
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21217831

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.