Rapamycin‐Conditioned Donor Dendritic Cells Differentiate CD4+CD25+Foxp3+ T Cells In Vitro with TGF‐β1 for Islet Transplantation

摘要: Dendritic cells (DCs) conditioned with the mammalian target of rapamycin (mTOR) inhibitor have been previously shown to expand naturally existing regulatory T (nTregs). This work addresses whether rapamycin-conditioned donor DCs could effectively induce CD4+CD25+Foxp3+ Tregs (iTregs) in cell cultures alloantigen specificities, and such vitro-differentiated iTregs control acute rejection allogeneic islet transplantation. We found that BALB/c bone marrow-derived (BMDCs) pharmacologically modified by mTOR had significantly enhanced ability recipient origin (C57BL/6 (B6)) vitro under Treg driving conditions compared unmodified BMDCs. These vitro-induced exerted donor-specific suppression vitro, prolonged graft survival vivo RAG−/- hosts upon coadoptive transfer T-effector cells. The expanded preferentially maintained Foxp3 expression draining lymph nodes. Finally, were further able endogenous naive convert conclude BMDCs can be exploited for efficient differentiation antigen-specific iTregs. Such vitro-generated are rejection.