The effect of changes in the innate and adaptive immune compartment within the renal allograft on graft outcome

Organ transplantation has become the treatment of choice for patients with organ failure. Novel and potent immunosuppressive drugs have become available, and have significantly reduced the incidence of acute rejection and improved short term organ survival. However, long-term graft survival hasn’t improved in parallel over the past decades and it is well established that ongoing destruction of the transplant by the recipient’s immune system continues to be a major contributor to graft loss. Immunosuppressants only provide aspecific suppression of the immune system and are also associated with significant side effects, among others damage of the renal transplant. Therefore, there is a continuing interest in transplantation without the need of long-term immunosuppression (or induction of transplantation tolerance) by using regulatory immune cells or influencing tolerogenic molecular pathways. In the last decade, several regulatory cell populations and tolerogenic pathways have been identified in murine models. In this project, we will describe the changes in immune cells and immune gene expression within the allograft using innovative techniques in a longitudinal manner, and the results will be correlated with changes seen in the peripheral blood and patient outcome. This will identify the relevant regulatory immune cell populations in organ transplantation and help us designing future tolerance-inducing studies in patients suffering from organ failure.