INTRODUCTION The introduction of triple-therapy regimens that include a calcineurin inhibitor, steroids, and azathioprine (AZA) or mycophenolate mofetil (MMF) greatly reduced the risk of acute rejection in renal transplantation. However, the long-term use of both calcineurin inhibitors and steroids is associated with serious toxicities that ultimately impact patient and graft survival. Minimisation of chronic immunosuppression is therefore of paramount importance to improve patient and graft survival. Thus, the quest for strategies inducing specific immune hyporesponsiveness or even tolerance - ideally via short-term interventions that would target only the pathogenic immune response and leave the protective host immune response unimpaired - has provided a "holy grail" for transplant immunologists.