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Last Updated: 2001-04-23 13:55:54 EDT (Reuters Health)
By Megan Rauscher
WESTPORT, CT (Reuters Health) - In a rat model, Australian researchers have shown that administration of leukocytes from the organ donor at the time of transplantation of a kidney or liver leads to long-term acceptance of these organs that would normally be rejected.
Dr. G. Alex Bishop and colleagues from the Royal Prince Alfred Hospital in Camperdown, New South Wales, report their finding in the April 15th issue of The Journal of Immunology.
"Previous studies have shown that donor leukocytes should be administered at least a week before transplantation to be effective," Dr. Bishop told Reuters Health. However, "pre-transplant administration of donor cells, in the form of blood transfusion, which was used extensively in early clinical transplantation prior to the modern era of immunosuppression, leads to a number of clinical problems that are avoided by administration at the time of transplantation."
For example, pretransplant infusion of donor leukocytes increases the risk of pre-sensitization of recipients leading to rapid rejection and the need to match the organ donor with the donor of the blood or leukocytes. The fact that cadaveric donors are the main source of transplanted organs limits the utility of pretransplant donor leukocyte administration.
In their paper, Dr. Bishop and colleagues report that administering donor leukocytes immediately after the transplant operation induced long-term acceptance of completely MHC-mismatched rat liver and kidney transplants.
"A further finding that is clinically relevant is that donor leukocyte-induced acceptance of kidney transplants is associated with rapid and extensive activation of the recipient's rejection response leading to the apparent exhaustion of this response," Dr. Bishop said. "This is important in understanding how to find treatments that will synergize with donor leukocyte administration to promote acceptance of the transplanted organ," he added.
The researcher believes that some immunosuppressive drugs may interfere with the immune activation that is closely associated with donor leukocyte-induced acceptance and may thus inhibit acceptance. "This means that immunosuppressive drugs will need to be screened in future to examine their effects on acceptance," he said.
J Immunol 2001;166:5258-5264.
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