Research Group

  • Dr. Thomas Wekerle, Principal Investigator
  • Prof. Megan Sykes, Research Associate


  • Vienna General Hospital, Vienna, Austria


  • Tolerance through Hematopoietic Cell Transplantation with Costimulation Blockade

The lifelong non-specific immunosuppressive drug therapy that all transplant recipients currently have to take allows good short-term results. Long-term graft survival, however, is severely limited by episodes of drug-resistant acute and chronic rejection and drug-related side effects. The induction of donor-specific immunological tolerance is therefore a long-sought goal in order to re-educate a patient’s immune system so that it accepts the "foreign" organ like own tissue without the use of chronic immunosuppressive drugs. It has been known for some time that the transplantation of donor bone marrow together with the organ graft allows the induction of robust tolerance. The clinical application of this concept has been inhibited, however, in large part by the toxicity of the recipient conditioning required for successful conventional allogeneic bone marrow transplantation (BMT).

Recently, a mouse model of allogeneic BMT using very high numbers of bone marrow cells and two new costimulation-blocking antibodies has been developed which, for the first time, avoided all cytotoxic (i.e. cell-destructive) recipient conditioning. This very mild protocol holds great promise for clinical tolerance induction in the future, but currently two main factors limit its clinical applicability: 1) the amount of bone marrow cells required cannot be obtained from one human donor, and 2) it is successful only in approximately half the treated mice. Mobilized peripheral blood stem cells (mPBSC) are routinely used for transplantation for hematological indications and offer the advantage that very high numbers of hematopoietic cells can be harvested from a living donor. mPBSC differ, however, in several important respects from bone marrow cells.

The proposed project, therefore, aims to achieve the following: 1) to induce tolerance through the transplantation of clinically obtainable amounts of mPBSC with costimulation blockade; 2) to improve reliability by transiently using immunosuppressive drugs; and 3) to identify and use the donor cell population which is responsible for one of the main tolerance mechanisms in this protocol, namely the peripheral deletion of donor-reactive T cells.

The goal of these studies is to develop a clinically applicable protocol for tolerance induction in living- (un)related kidney transplantation. Such a protocol would be expected to substantially improve graft survival and morbidity after organ transplantation.