Research Group

  • Dr Erik Finger, Principal Investigator
  • Prof. Bruce Blazar, Research Collaborator

Location

  • University of Minnesota, Minneapolis, USA

Title

  • Prevention of Transplant Rejection in Mice with Human Immune System

Transplantation is a life-saving approach to treat a wide number of human diseases that result in failure of the heart, lungs, liver, kidney, or intestines. It can also be used to treat diabetes and some forms of cancer. A major limitation of transplantation is the need for life-long immunosuppression. This immunosuppression is toxic to multiple organ systems and predisposes the transplant recipient to infections and cancers. Immunosuppression directly contributes to the shortened lifespan of both the transplanted organs and recipients. These complications have prompted an ongoing search for treatments that would be non-toxic but prevent transplant rejection while maintaining intact normal immune responses. This state of immune tolerance is the target of most research in the fields of autoimmunity and transplantation today.

We focus our research on a population of lymphocytes called regulatory T (Treg) cells. These Treg cells are able to specifically suppress the immune response to a variety of foreign tissues, but maintain the remainder of the immune system intact. We are engineering Treg cells that will prevent rejection of donor tissues, but not inhibit normal immune responses. One of the main limitations in studying these cells has been the lack of techniques to study the function of these human Treg cells in living organisms, apart from performing experiments in humans. We have developed an approach to study these cells in a humanized mouse. This mouse has an intact human immune system. Human insulin-secreting islet cell are transplanted into these mice and we are able to study the human immune response and rejection in a living model. We use advance microscopic techniques to directly visualize cellular interactions in rejecting islet transplants in living animals. This enables us to study the ideal features of Treg cells that are required to prevent transplant rejection and induce this state of tolerance. Findings resulting from these studies can be directly applied to the utilization of Treg cells to prevent rejection of organ transplants in humans.

Final Report