Researchers in Boston and Philadelphia are studying ways to make transplanted organs last longer but, ironically, the common immunosuppressant drug cyclosporine may stand in the way.
In two papers published on November 1 in Nature Medicine (1999;5:1298-1302 and 1999;5:1303-1307), Laurence A. Turka of the University of Pennsylvania and Terry B. Strom of Harvard Medical School and colleagues said that, in mice with heart transplants, the use of CTLA4Ig and CD40 ligand promoted T-cell apoptosis and prevented the growth of more destructive T cells. However, organ rejection increased when cyclosporine was added to the treatment regimen. In contrast, the use of rapamycin (Rapamune) preserved the apoptotic effect while acting as a general immunosuppressive drug.
In another article in the same issue (1999;5:1292-1297), Hans J. Schlitt and colleagues in Hannover, Germany, said that the small numbers of blood cells that are passed from donor to recipient during a transplant are vital for the induction of transplant tolerance. Their study was based on heart transplants in rats. If donor blood cells were removed from the recipient's circulation within the first two weeks after a transplant, the animals rejected the transplanted organ.
The same issue of Nature Medicine also carried a review article on transplantation tolerance by Herman Waldmann (1999;5:1245-1248). Despite a variety of stumbling blocks, he said: "Establishing tolerance induction as a viable alternative for immunosuppression after organ transplant is, however, a reasonable goal that can be achieved through cooperation between basic and clinical researchers, regulatory authorities and industry."
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