Research Group

  • Dr Jane H. Buckner, Principal Investigator
  • Dr Brad Stone, Co-Investigator

Location

  • Benaroya Research Institute, Seattle, USA

Title

  • Induction of Minor Histocompatibility Specific T Regulatory Cells as a Therapy of Transplant Rejection

Most human proteins vary slightly from one individual to another. When a tissue is transplanted, those variations that are present in donor tissue, but not in recipient tissue, are often recognized as ’foreign‘ by host immune cells. The host immune system then mounts an attack that, over time, will damage and destroy the transplanted organ in a process called chronic rejection. The long-term goal of this project is to ’re-educate‘ host immune cells to switch from recognizing the donor variations as ’foreign’, to recognizing them as ’self’, thereby blocking chronic rejection by the host immune system. The first step in this process is to identify some of the variations that are targeted by host immune cells. We will use a new ‘microarray’ technology to evaluate a large percentage of these variations by analyzing the DNA from both the donor and the recipient. We will then apply proven computer programs that can determine which of the variations unique to the donor organ can be detected by the immune system. Once these variations have been identified, we will make proteins that resemble the donor tissues to stimulate host immune cells known as ‘T regulatory’ cells. This stimulation will be done in a test tube under carefully controlled conditions. Using this approach, we have previously shown that we can grow T regulatory cells that will shut down an immune response. If we can make these cells respond to the protein variations that are unique to the donated organ, we may be able to develop therapies that will specifically shut down rejection of transplanted organs. These studies will analyze blood from patients receiving a kidney transplant, but if successful, the approach could be more generally applied to transplantation of any human tissue, including transplantation of human islet cells for treatment of autoimmune diabetes.

Progress Report
Final Report