Exceptional Acceptance

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Science  22 Feb 2008:
Vol. 319, Issue 5866, pp. 1013
DOI: 10.1126/science.319.5866.1013b

In 1960, Medawar and Burnet were awarded the Nobel Prize for Physiology or Medicine for showing that immunological tolerance to foreign grafts can be acquired. What this and many studies in animal models have shown since is that it is possible to “re-educate” the immune system of the recipient to the foreign antigens carried by the donor cells and grafts. The induction of full immune tolerance to transplanted organs has also been pursued in the clinic because this would dispense with the need for extensive immunosuppressive regimes currently used to prevent organ rejection.

Scandling et al. and Kawai et al. report cases of human kidney transplantation in which hematopoietic cells from the donor were co-transplanted with the organ, followed by distinct protocols of conditioning involving depletion of host cells. In the first study, this resulted in ongoing mixed chimerism; meaning that there were comparable proportions of donor and recipient hematopoietic cells circulating in the body. In the second study, the extent of chimerism was considerably less and was also transient. Nevertheless, in both clinical settings it was possible to discontinue immunosuppressive drugs without significant adverse responses to the grafted organs; furthermore, cellular evidence of immunological tolerance was detected. In a third study, Alexander et al. describe a female liver transplant patient in which a spontaneous switch occurred in the blood group and—because the donor was male—the sex of the circulating leukocytes. Impressively, the removal of immunosuppressive drugs, which was undertaken to resolve hemolytic anemia in the patient, resulted in complete chimerism (meaning that all hematopoietic cells were of donor origin) and long-term acceptance of the grafted liver. These three studies reveal that immunological acceptance of transplanted organs is a realistic goal worthy of further exploration. — SJS

N. Engl. J. Med. 358, 362; 353; 369 (2008).

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