- Dr. Paul S. Russell, Principal Investigator
- Dr. Joren Madsen, Co-Investigator
- Dr. Robert Colvin, Co-Investigator
- Mr. Harris S. Rose, Research Associate
- Ms. Catharine M. Chase, Research Associate
- Dr. Megan Sykes, Collaborator
- Dr. David Sachs, Collaborator
- Massachusetts General Hospital, Boston, USA
- Cellular Mechanisms of Cardiac Allograft Vasculopathy (CAV) in Tolerant and Immunodeficient Mice
These experiments are designed to clarify a new mechanism we have recently discovered for the development of coronary artery disease in transplanted hearts. We were surprised to find that impressive disease can occur in mouse hearts transplanted to incompatible recipients even though they had been made completely inactive (“tolerant”) to the known antigens presented by the transplants. Transplants between identical animals never became diseased. Similar results were found with hearts transplanted to mice genetically incapable of any kind of conventional immune response. We feel that so-called “innate” immunity, which can operate quite separately from the usual rejection process, may contribute importantly to this process, a process that seriously limits the survival of many transplanted organs.
The proposed experiments involve performing heart transplants, by microsurgical methods, between special strains of inbred mice. These would include strains in which “natural killer” cells (NK) are inactivated genetically or in which such cells are neutralized by specific antibodies to them. We can also visualize NK, and other important cells, in microscopic sections of the coronary vessels with monoclonal antibodies directed toward them. We hope to define precisely the involvement of “natural killer cells” and certain cytokines in this process and thereby open up new approaches for controlling this pathological process much more effectively.