Abstract: Objective This study aimed to evaluate the effect of a sequential treatment on small bowel transplantation(SBT) allograft survival and attempted to elucidate the underlying mechanisms to prevent chronic rejection(CR). Methods Sequential treatment with rapamycin (Rapa) following a FK506 pretreatment was administered to control CR in rat orthotopic SBT model. The recipients were sacrificed for evaluation of CR by morphological and immunohistochemical analysis. The production of antidonor isotype specific antibody was quantified by flow cytometry. Results In control group, 79% recipients developed severe vasculopathy and parenchymal fibrosis and died of CR around 90 postoperative day. With sequential treatment, 91.7% recipients survived, showed reduced severity of vasculopathy, markedly reduced fibrosis in the mesentery, and inhibition of the production of the Th1 and Th2 associated isotype specific antibodies. Conclusion The sequential treatment was effective in the control of CR and dramatically prolonged rat allograft survival, and may contribute in a clinical setting towards better outcomes in SBT.

Key words: small bowel transplantation, chronic rejection, pathology, immunological tolerance