The role of T-cell apoptosis in transplantation tolerance

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Organ transplantation is the treatment of choice for patients with end-stage heart, lung, liver or kidney failure and there have been spectacular improvements in the early success of these procedures. However the 10 year graft survival rate has not changed much in the past 15 years. One way of overcoming this problem is to manipulate the immune system so that the transplant is accepted indefinitely. This is called tolerance and it works by giving intense immunosuppression for a short period so that the transplant is accepted indefinitely without the need for long term immunosuppression. The immune mechanism responsible for this phenomenon is complex and is poorly understood. This project aims to study the early events in the immune system that leads to transplantation tolerance. In particular, factors involved in programmed cell death in white blood cells will be studied. Specially bred mice that have blocks in the cell death mechanisms will used to determine what effects these blocks have on the ability to induce tolerance. Other mice that have been genetically altered to allow their white cells to be tracked will be used to study the fate of these cells. If the mechanisms involved in tolerance induction are better understood, then it will be possible to design specific immunosuppressive drugs that will be used to produce tolerance in transplant patients.