Chronic rejection or tolerance after liver small bowel transplantation

Background: Small bowel transplantation requires higher immunosuppression (IS) than e.g., liver transplantation, but without comparable results. The tolerogenic effect of a liver allograft towards the small bowel after combined liver/small bowel transplantation is controversially discussed. Methods: In this study two new models were developed for combined liver/small bowel transplantation in rats: LHDTx, orthotopic liver/heterotopic small bowel transplantation; LODTx, orthotopic liver/orthotopic small bowel transplantation. Results: Compared to isolated heterotopic small bowel transplantation (HDTx) in the BN-LEW strain combination liver allografts changed acute rejection after HDTx in 70% of the cases into long-term acceptance of the combined allograft (LHDTx) without IS. However, 10% of these long-term survivors developed histological signs of a chronic rejection. Orthotopic small bowel transplantation (ODTx) with IS (2 mg FK506/kg/d, day 0 - 5) resulted in chronic rejection of the small bowel allograft, which was prevented by the liver allograft (LODTx) in 80% of the cases under a significant lower dosage of IS (0.5 mg FK506/kg/d, day 0-5). The development of specific tolerance after LHDTx and LODTx was proved by indicator heart transplantation. Conclusion: Both models, LHDTx and LODTx, demonstrate for the first time in rats the tolerogenic effect of the liver towards a small bowel allograft. Kupffer cells, initially increased in the liver allograft, may play a role in modulating the immune response of the recipient.