Research Group

  • Dr Masato Imai, Principal Investigator
  • Dr Simon C. Robson, Co-Investigator
  • Dr Beat Kunzli, Research Assistant
  • Dr Csizmadia Vilmosne, Technician


  • Beth Israel Deaconess Medical Center, Boston, USA


  • NTPDase-1/CD39 Ameliorates Transplant Arteriosclerosis

Advances in immunosuppression have largely controlled acute allograft rejection and organ failure after clinical transplantation. However, delayed graft loss still poses a barrier to prolonged organ survival. Indeed, graft survival rates after one year have not improved over the past three decades. Graft loss is due to chronic rejection and the development of transplant arteriosclerosis (TA). TA is characterized by formation of diffuse thickening of the inside of blood vessels. Donor: recipient mismatch and history of acute rejection are risk factors for chronic rejection. However, reinforcement of conventional immunosuppression does not prevent TA. Certain white blood cells, called natural regulatory T cells, appear to inhibit inflammation and vascular injury in atherosclerosis models in mice.

There are chemicals called nucleotides that are important mediators within the vasculature and immune system. NTPDase-1/CD39 is the dominant vascular and immune ecto-enzyme that removes these nucleotides, e.g., ATP. However, this biochemical activity is lost from the vasculature during injury and in graft rejection. CD39 up-regulation is seen in working grafts. We have previously shown that viral-mediated overexpression of CD39 in cardiac grafts limits vascular injury and suppresses thrombosis. Transgenic mouse cardiac allografts overexpressing CD39 are also resistant to antibody rejection responses and platelet sequestration.

Our preliminary data indicate that CD39 overexpression in allografts, soluble NTPDase protein treatment and recombinant CD39 adenovirus vectors significantly suppress intimal hyperplasia. Certain white blood cells, called natural regulatory T cells, appear to inhibit inflammation and vascular injury in conventional atherosclerosis models in mice. CD39 is a selective surface marker of such regulatory T cells and CD39 null cells are defective in that they cannot block allograft rejection.

This proposal will elucidate whether NTPDase-1/CD39 has beneficial effects on the development of TA. We propose that NTPDase-1/CD39 supplementation will suppress TA and control elements of chronic rejection.

Final Report