"It is these first few days and weeks after transplantation when the seminal mechanism of organ engraftment and of acquired tolerance to donor tissue occur," said Dr. Starzl, professor of surgery at the University of Pittsburgh School of Medicine.
What makes better sense, even though it may seem counterintuitive to most in the field, is to allow the immune activation against the donor organ to occur, but in a subdued fashion so that the clonal deletion of the T cells is both more complete and long lasting. Therefore, it is important to weaken the T cell response before the antigen the donor organ is introduced, he explained.
In more than 250 recipients of liver, kidney, kidney/pancreas, intestine and multivisceral transplants, the University of Pittsburgh team administered a single dose of rabbit anti-thymocyte globulin, which depletes T cells, before surgery. Then one day after transplantation, when that immune response had begun, surgeons began giving tacrolimus as the only anti-rejection drug and at much lower doses than is typical.
In 1962 and 1963, while at the University of Colorado, Dr. Starzl treated his nine living-related kidney transplant patients in a similar fashion. One to two weeks before transplantation, the patients received azathioprine, a drug that inhibits the growth of T cells. The same drug was given after transplantation, and prednisone was administered only for the treatment of reject
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Contact: Lisa Rossi
412-647-3555
University of Pittsburgh Medical Center
26-Aug-2002