- Prof. Alfred L.M. Bothwell, Principal Investigator
- Yale University, School of Medicine, New Haven, USA
- Characterization of molecules important for preventing rejection of transplanted pig organs
The only successful method of treatment of certain diseases especially of the kidney and heart is by organ transplantation. In addition, while many patients undergoing dialysis do survive for a long period of time there is significant mortality. An enormous improvement in lifestyle can be achieved by transplantation. Unfortunately, the supply of donor human organs can not even begin to meet the current needs of patients and one would anticipate that it never will. Therefore, development of alternative strategies that would meet this need would be of enormous benefit to society.
At the current time by far the most favoured source for donor organs is the pig. Indeed, there is not any other contender given the potential advantages of supply and ability to create transgenic animals. In the last few years, the biologic basis for the rapid rejection of potential porcine organs has been defined. Natural antibodies in humans react with molecules on porcine cells that result in destructive action by the complement system. Strategies have now been devised using complement inhibitors that appear to overcome this major short-term biologic barrier.
The long term survival of porcine grafts will require a thorough understanding of the cellular immune responses that occur in vivo. The primary regulators of the human anti-porcine response that must be characterized are distinct populations of T lymphocytes. T cells recognize proteins on porcine cells that promote direct binding as well as signal the T cells that they are foreign. The focus of this proposal is the identification and characterization of these porcine cell proteins that affect the immune response of human T cells. This information is required for development of either small molecule inhibitors, transgenic porcine organs of humanized antibody reagents that will enhance the survival of xenografts.