The current organ shortage in transplantation medicine stimulates the exploration of new strategies to expand the donor pool including the utilization of living donors, ABO-incompatible grafts and possibly xenotransplantation. Our research focuses on: 1. Preformed natural antibodies, such as anti-A/B histo-blood group antibodies, mediate hyper-acute graft rejection in solid organ transplantation but do not seem to affect the outcome of hematopoietic stem cell transplantation (HSCT). Thus, ABO-incompatible HSCT may serve as an in vivo model to study the immunological mechanisms leading to successful carbohydrate-antigen mismatched transplantation. Our goal is to analyze the mechanisms such as deletion or anergy of B cells and understand the mechanisms of B cell tolerance induction in recipients of solid organ transplantation. 2. Cellular immune responses represent a major obstacle to successful transplantation. A major challenge in organ transplantation is to impair recipients'potential to reject the transplanted organ while preserving its function and limit the adverse effect of immunosuppression on patients' overall survival. The immunosuppressive regimens are mostly assessed on T and B lymphocytes but remain poorly explored with regard to post-transplant function and reconstitution of other immune effector cells, such as natural killer (NK) cells. 3. Porcine and human endothelial cells (EC) share the expression of receptors involved in the adhesion and transmigration of leukocytes into the graft. The interactions between human leukocytes and porcine EC depend on the existence of intact cross-species receptor-ligand interactions. Blocking of the crucial receptors for adhesion and transmigration, in combination with prevention of hyperacute rejection, may lead to the clinical feasibility of pig-to-human xenotransplantation. The goal of this project is to define the mechanisms of interactions between human leukocyte subsets and porcine EC in chemotaxis, adhesion, and transendothelial migration.

Nephrology