Ex vivo expanded human regulatory T cells delay islet allograft rejection via inhibiting islet-derived monocyte chemoattractant protein-1 production in CD34+ stem cells-reconstituted NOD-scid IL2rγnull mice.

摘要: Type 1 diabetes mellitus (T1DM) is an autoimmune disease caused by immune-mediated destruction of insulin-secreting β cells the pancreas. Near complete dependence on exogenous insulin makes T1DM very difficult to control, with result that patients are exposed high blood glucose and risk diabetic complications and/or intermittent low can cause unconsciousness, fits even death. Allograft transplantation pancreatic islets restores normoglycemia a surgical complications. However, although successful immediately after transplantation, progressively lost, most requiring within 2 years post-transplant. Therefore, there urgent requirement for development new strategies prevent islet rejection. In this study, we explored importance human regulatory T in control allograft We developed pre-clinical model reconstituting NOD-scid IL2rγnull mice cord blood-derived CD34+ stem demonstrated engrafted immune system mediated rejection islets, their survival was significantly prolonged following adoptive transfer ex vivo expanded Tregs. Mechanistically, Tregs inhibited infiltration innate CD4+ into graft down-regulating graft-derived monocyte chemoattractant protein-1. Our findings might contribute clinical Treg therapy also show first time cells-reconstituted mouse could be beneficial investigating immunity vivo.