Research Group

  • Dr Joren Madsen, Principal Investigator
  • Dr Tsutomu Hirohashi, Research Associate
  • Ms Catharine Chase, Sr. Technician
  • Dr Paul S. Russell, Collaborator
  • Dr Robert B. Colvin, Collaborator

Location

  • Massachusetts General Hospital, Boston, USA

Title

  • How the Innate and Adaptive Immune Systems Interact to Prevent Long-term Allograft Survival

After years of relative neglect in the field of solid organ transplantation, NK cells, part of the innate immune system, are being recognized as active participants in the acute and chronic rejection of solid tissue grafts. They appear to contribute to acute organ rejection indirectly, by activating or providing help to effector cells such as cytotoxic and helper T cells. They appear to contribute to chronic rejection by suppressing the function of natural regulatory T cells. These findings have direct clinical relevance as NK cells are not effectively targeted by current immunosuppressive therapy, including cyclosporine. Indeed, this may explain why cardiac allograft vasculopathy, a primarily MHC-driven alloimmune process, still occurs in heavily immunosuppressed recipients. Ultimately, NK cell inactivation/depletion may prove uniquely beneficial to human recipients of solid organ allografts, both those receiving chronic immunosuppression as well as to future patients undergoing tolerance induction.

Progress Report
Final Report