Abstract
There is a clear need to develop strategies to induce tolerance without the need of chronic immunosuppression in transplant recipient and in patients with autoimmunity. Adoptive T regulatory cell (T
reg
) therapy offers the potential of long-lasting protection. However, based on results of clinical trials so far with
ex vivo
expanded autologous T
regs
in type 1 diabetic (T1D) patients, it seems unlikely that single immunotherapy with T
reg
infusion without immunomodulation regimens that promote stable donor T
reg
engraftment and persistence would afford truly significant clinical benefit. Combination therapies could provide improved outcomes with consideration of the fundamental factors required for T
reg
generation, homeostasis, and function to promote long-term donor T
reg
persistence to provoke beneficial therapeutic outcomes.