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

Abstract

PurposeAllograft 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. MethodsIDO-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 neovascularization, 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. ResultsThe 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 neovascularization, 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 significantly reduced after transplantation. ConclusionOur 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.