Indoleamine 2, 3-dioxygenase-transfected bone marrow-derived mesenchymal stem cells promote corneal allograft survival by inhibiting T cell proliferation: A rat study

Purpose: Allograft rejection is still the main cause of corneal transplantation failure. Therefore, we investigated the role of indoleamine 2,3-dioxygenase (IDO)-transfected bone marrow-derived mesenchymal stem cells (IDO-BMSCs) in corneal allograft rejection in rats.Methods: IDO-BMSCs were constructed and co-cultured with CD4+CD24- T cells to detect their effects on the proliferation of CD4+CD25-T cells in vitro. A corneal allograft rat model was used to confirm our in vitro and in vivo observations. Therefore, IDO-BMSCs were injected directly into the recipient's conjunctiva on the day of corneal transplantation and on day 5 after operation. Corneal graft rejection indices, including corneal neo-vascularization, opacity, and edema, were measured for up to 14 days after transplantation. The recipients' cervical lymph nodes and peripheral blood were collected to test the role of IDO-BMSCs in immune cells using flow cytometry. Results: The lentivirus-mediated IDO gene was successfully transfected into BMSCs, which stably secreted the IDO protein. The proliferation of CD4+CD25-T cells was significantly inhibited after their co-culture with IDO-BMSCs. Subconjunctival injection of IDO-BMSCs into corneal allografts of rats effectively reduced graft neo-vascularization, promoted allograft survival, and induced immune tolerance. Both CD4+ and CD8+ T cells in the local lymph nodes and peripheral blood, along with CD4+CD25-T cells in the local lymph nodes, were signifi-cantly reduced after transplantation.Conclusion: Our results suggest that IDO-BMSC treatment enhances the direct immunomodulatory effect of corneal allograft transplants in rats, promoting corneal allograft survival by inhibiting the proliferation of CD4+, CD8+, and CD4+CD25-T cells. Therefore, modification of BMSCs by lentivirus-mediated IDO gene transfection may provide a novel strategy for controlling corneal allograft rejection.