The Overriding Problem

Common To All Transplantation

Except for transplants between identical twins, all transplant donors and recipients are immunologically incompatible. This biologic incompatibility is a barrier that causes the recipient to try to destroy or reject the new organ, tissue or cells. In graft-versus-host disease, rejection occurs when the transplanted donor cells try to destroy or reject recipient tissues. (see Fig. 2)

• Rejection episodes may be mild or severe but, with time, will lead to graft failure or patient death.
  
  
• As surgical methods to transplant grafts improve, rejection becomes the major cause of graft failure.
  
  
• Of those awaiting organ transplantation, more than one-fourth of patients have already had at least one graft failure.
  
  
• Immunosuppression - the current therapy to prevent and treat rejection - increases the incidence of infection and cancer.

• Develop better drugs for immunosuppression.
  
  
• Design methods to prevent rejection that do not require generalized immunosuppression, that has adverse side effects. This is known as donor-specific tolerance.
  
  
• Control recognition and rejection of transplanted tissues by identifying the mechanisms involved.

• Determined the mode of action of some of the most important immunosuppressive agents, such as cyclosporine.
  
  
• Developed a detailed understanding of the targets of rejection.
  
  
• Ongoing development and evaluation of several new immunosuppressive agents with the potential to be more effective while having fewer undesirable side effects.
  
  
• Ongoing development and evaluation of new methods to induce donor-specific tolerance.
  
  
• Demonstrated significant improvement in one-year graft survival in kidney transplant recipients treated with donor bone marrow to induce tolerance.