Potential T regulatory cell therapy in transplantation: How far have we come and how far can we go?

Graft survival has been lately improved by the introduction of efficient immunosuppressive drugs. However, late graft loss caused by chronic rejection and the side effects of long-term immunosuppression remain major obstacles for successful transplantation. Operational tolerance, which is defined by the lack of acute and chronic rejection and indefinite graft survival with normal graft function in the absence of continuous immunosuppression, represents an attractive alternative. Nevertheless, tolerance after allogeneic transplantation is commonly considered the 'mission impossible' for both immunologists and clinicians. One of the mechanisms involved in tolerance is the suppression of graft-specific alloreactive T cells, which largely mediate graft rejection, by regulatory T cells (Tregs) or by soluble factors produced by Treg cells. With this review, I will make an effort to collect and describe the significant studies performed in transplanted patients, and not in animal models or in in vitro systems, with the attempt to: (i) understand how tolerance is achieved, (ii) define whether and how Treg cells influence transplant tolerance, (iii) describe the first clinical trials with Treg cells in humans (i.e. how far have we come) and (iv) predict the future of Treg cell-based therapy in humans (i.e. how far can we go).