Research Group

  • Dr. Irma Joosten, Principal Investigator
  • Dr. Luuk Hilbrands, Co-Investigator
  • Dr. Elly van de Wiel-van Kemenade, Co-Investigator


  • University Medical Center St. Radboud, Nijmegen, The Netherlands


  • Cell Therapy to Prolong Graft Survival

Transplantation of organs (e.g. of hearts, lungs, livers and kidneys) is an important therapy for patients in whom the function of these organs has been lost. To prevent rejection of the transplant, immunosuppressive drugs are used that successfully suppress T-cell responses, but which have the common disadvantage that they also inhibit natural resistance against infections and malignancy. Furthermore, the different immunosuppressive drugs have a number of specific side effects. Consequently, new ways are being sought which allow for the induction of specific tolerance to the donor organ. In the past few years the attention has been directed to the inhibition of so-called costimulatory signals, important in T-cell activation. Recognition of (foreign) antigen by T-cells in the absence of a costimulatory signal results in the generation of so-called anergic T-cells. These cells are able to specifically suppress donor-directed immune responses. Prolonged graft survival has already been achieved by the in vivo administration of antibodies directed against these costimulatory molecules in animal models. However, administration of mouse or even humanised antibodies to a human transplant recipient has several drawbacks, such as non-specific effects on the immune system. We have now developed a system that allows us to generate anergic T-cells ex vivo with the aid of antibodies against costimulatory molecules. These anergic T-cells possess regulatory and so-called infectious properties, which means that the anergic state can be transferred to other T-cells, that in turn will become tolerant to the transplanted organ. In this project we want to study the in vivo immunosuppressive capacity of anergic T-cells using a mouse heart transplant model. To this purpose ex vivo anergised T-cells of a recipient mouse strain, tolerised against the donor organ prior to transplantation, will be infused at different time points around transplantation. These cells are expected to confer their immunosuppressive function in a donor-specific way. Particularly in combination with immunosuppressive drugs that allow tolerance induction we expect this treatment to be of potential use to human clinical practice, especially for organ (kidney) transplantations involving living (related) donors.