Analysis of simultaneous allotransplantation of small intestine and liver

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The first series of experiments examined the effect of intra-muscular(im) administration of FK506 on small intesitine allo-graft survival. DA and LEW rats were used as small intestine donors and recipients. FK506 (0.3mg/kg, 1.0mg/kg or 2mg/kg) was given im for 14 days after transplantation. The results clearly demonstrated that the rejection of small intestine allograft was suppressed by FK506 at the dosage of 2.0mg/kg per day, whereas, as a complication of this drugs, all rats died of pneumonia. In order to diminish the requirements for high doses of FK506 in recipients of small intestine allograft, we tried to investigate the effect simultaneous allotransplantation of small intestine and liver. However, recipients died of infection. We changed the protocol to analyze the effect of donor-specific transfusion (DST) and FK506 on small intestine allotransplantation. Recipients (LEW) received 1.5 ml of freshly drawn DA blood iv on day -8 with respect to grafting ( day 0 ). FK506 was administered at a dose of 1.0mg/kg per day from day -8 to day -4, and at 0.3mg/kg per day from day 0 to day +14. The results clearly demonstrated that FK506 combined with DST is effective to prevent acute rejection. Longterm allograft survival could be obtained by conditioning with combined DST and low-dose FK506. To test for in vivo effects of DST+FK506 on T cell function , CTL and IL-2 production were tested in rats treated with DST+FK506. The results suggested that DST+FK506 resulted in selective inhibition of anti-DA T-cell responses without suppressing T-cell responses to third party alloantigens.