Research Group

  • Prof. Giuseppe Remuzzi, Principal Investigator
  • Dr. Ariela Benigni, Co-Investigator
  • Dr. Marina Noris, Co-Investigator


  • Mario Negri Institute for Pharmacological Research, Bergamo, Italy


  • Donor Peripheral Blood Mononuclear Cells Homing the Thymus of Recipients to Induce Graft Tolerance

The success of clinical organ or tissue transplantation currently depends on the use of non-specific immunosuppressive drugs. However, long-term immunosuppression increases the risk of life-threatening infections and cancer in transplant recipients, and patients receiving immunosuppressive drugs still experience chronic graft rejection. To eliminate or reduce the need for long-term immunosuppressive drugs, a strategy would be to reprogram the host's immune system to selectively ignore, or tolerate, the transplant without compromising protection against pathogens. This would allow the induction of donor antigen-specific immunologic unresponsiveness.

In an effort to find strategies less toxic than current conditioning protocols to induce transplantation tolerance, we found that pretransplant donor peripheral blood mononuclear cell (PBMC) infusion allowed indefinite kidney allograft survival in rats. Graft tolerance correlated with the presence of donor cells in the host thymus (microchimerism). These findings provide the basis for exploring the possibility that enhancing migration of donor cells into the host thymus would favour the development of donor-specific transplantation tolerance. We hypothesised that this could be accomplished by transfecting donor cells with genes encoding molecules, such as CD44 and/or CCR9, that are critical for cell migration into lymphoid organs, including the thymus.

Since dendritic cells (DCs) represent the ideal donor cells for transfection, in that under naive conditions they express variable levels of CD44 and very low levels of CCR9 molecules on their surface, and given the fact that we previously found that induction of graft tolerance occurs through migration of donor cells into the host thymus, donor transfected DCs will be used to test our hypothesis. From this series of studies in rodent models of kidney and heart transplantation we expect to document that donor DCs transduced with CD44 and/or CCR9 genes allow the development of graft tolerance by homing to the host thymus where they activate donor-specific tolerogenic pathways.