Approaching tolerance in transplantation.

Basic research has provided substantial encouragement that tolerance processes may be harnessed to the benefit of organ transplants. The goal of achieving mixed chimerism to ensure a robust tolerance, however elegant, may yet prove to be too complex and, consequently, risky as a procedure to compensate for the breadth of genetic differences, and prior immunological experiences of donor and host. Tolerance through regulation may prove to be easier to generate, but insufficiently robust to maintain. In the end the chosen protocol will be one that is simple, cheap and can guarantee patient compliance. Pragmatically, such a protocol need not be one aimed at clear-cut drug-free tolerance, but rather one which is trouble free. This could end up as a combination of partial tolerance (where tolerance processes have been harnessed) induced through a short-term treatment, in conjunction with easily tolerated maintenance therapy with select immunosuppressive drugs. Perhaps to the patient, the holy grail of tolerance is not as important as the complete assurance that the graft will survive and continue to function in all circumstances.