Just 1 week after the nobel prize recognized key discoveries on regulatory T cells (Tregs), we contribute our study on the preclinical development of allogeneic 'off-the-shelf' Treg appraoches. Despite their inherent immunosuppressive function, allogeneic Tregs did not prevent their own immune rejection in immunocompetent models. Consequently, either stringent HLA matching or precise HLA gene editing were required for the optimal function of allogeneic Tregs in transplantation models. Herein, the described gene editing strategy provides a route toward 'off-the-shelf' cell therapies using the immune system's peacekeapers to regulate pathogenic immune responses in autoimmunity, transplantation or tissue replacement therapy. The study resulted from an international collaboration within the ReSHAPE consortium between Charité – Universitätsmedizin, Berlin Institute of Health and University of Oxford; and benefited from contributions from Baylor College of Medicine, USA.