Research Group

  • Dr. Li Zhang, Principal Investigator
  • Dr. Myron Cybulsky, Co-Investigator


  • University Health Network, Toronto, Canada


  • Mechanisms Involved in Prevention of Donor-Specific Cardiac Allograft Rejection by Regulatory T Cells

Organ transplantation is a potent therapeutic modality for patients with end-stage organ failure. While it is generally successful, there are still a number of significant problems that affect all transplant patients. Most graft recipients have to take multiple immunosuppressive medications for as long as the transplant is functioning. These medications are expensive and have toxic side effects. Transplant patients also have a high incidence of opportunistic infections and malignancies due to suppression of the immune system of recipients by non-specific immunosuppressive drugs. Moreover, use these drugs does not ensure permanent survival of the transplanted organs. Most transplanted organs are eventually rejected. The major clinical goal of organ transplantation is to induce long-term graft survival without the need for non-specific toxic immunosuppressive drugs.

Recent work from our group demonstrated that exposure of recipient to donor white blood cells under appropriate conditions leads to activation and expansion of recipient regulatory T cells. We have further demonstrated in mice that these activated regulatory T cells can migrate to transplanted organs and tissues, specifically inhibit anti-graft immune responses, and enhance donor-specific skin graft survival.

In this proposal, we will investigate how to effectively activate recipient regulatory T cells to prevent cardiac graft rejection in mouse models. We will delineate the mechanisms involved in regulatory T cell migration, and antigen-specific suppression. We will also determine whether regulatory T cells can be identified and activated in humans. The results from these studies will enhance our understanding of the mechanisms of antigen-specific suppression. They will also provide a basis for a trial using regulatory T cells for the prevention of allograft rejection and the treatment of autoimmune diseases.