Research Group

  • Prof. Joost van Meerwijk, Principal Investigator
  • Dr. Paola Romagnoli, Research Associate


  • INSERM U563, Purpan Hospital, Toulouse, France


  • Development of a Cell-Based Therapy against Short-Term and Long-Term Graft Rejection

Despite availability of very efficient immunosuppressive drugs, organ transplantation is still severely hindered by long-term graft rejection and serious toxicity as well as by the side effects of the drugs. Development of highly specific and durable therapies would therefore be of significant benefit to transplant recipients. We propose to develop a cell therapy for the induction of graft tolerance with these crucial properties.

We have recently published that rejection of bone-marrow grafts can efficiently be inhibited with a newly discovered population of regulatory
T lymphocytes in mice. Our more recent data indicate that also transplanted hearts and skin can be protected using this regulatory T cell population in mice. Importantly, in contrast to immunosuppressive drugs, regulatory T cell-induced tolerance is specific (and therefore allows for immunological protection against infections) and durable (we have not observed so-called “chronic rejection”).

It will now be important to transpose the protocol allowing for the induction of transplantation tolerance with regulatory T cells to humans. First of all, it will be important to identify the immunosuppressive mechanisms responsible for the inhibition of graft rejection in our mouse model. Then, a logistic problem inherent to the human setting will need to be solved. To this end, we will study how immunosuppressive drugs can initially be used to inhibit rejection and later replaced with regulatory T lymphocytes. Finally, we will study the potential of human regulatory T lymphocytes to inhibit human graft rejection in mice harboring a “humanized” immune system. The described project will allow us to evaluate the feasibility of a regulatory T cell-based therapy for human organ transplantation. This therapy should lead to life-long graft acceptance in absence of generalized immunosuppression.

Final Report