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Regulatory T cells are essential to maintain immune homeostasis and prevent autoimmunity. Therapy with  in vitro  expanded human nT Regs  is being tested to prevent graft versus host disease, which is a major cause for morbidity and mortality associated with hematopoietic stem cell transplantation. Their usefulness in therapy will depend on their capacity to survive, migrate appropriately and retain suppressive activity when introduced into a transplant recipient. The lack of a suitable animal model for studying the  in vivo  reconstitutive capability of human nT Regs  is a major impediment for investigating the behavior of adoptively transferred nT Regs   in vivo . We show that injection of a plasmid encoding human IL-2 is necessary and sufficient for long term engraftment of  in vitro  expanded nT Regs  in NOD-SCID IL2rγc null  mice. We also demonstrate that these  in vivo  reconstituted T Regs  traffic to different organs of the body and retain suppressive function. Finally, in an IL-2 accelerated GVHD model, we show that these  in vivo  reconstituted T Regs  are capable of preventing severe xenogenic response of human PBMCs. Thus, this novel ‘hu-T Reg  mouse’ model offers a pre-clinical platform to study the  in vivo  function and stability of human nT Regs  and their ability to modulate autoimmune diseases and GVHD.

Long-Term Engraftment of Human Natural T Regulatory Cells in NOD/SCID IL2rγcnull Mice by Expression of Human IL-2