A study of tolerance induced by liver transplantation on intestinal graft in the rat]

In some strain combinations of rats, orthotopic liver transplantation (OLT) permits long-term donor-specific survival of fully allogeneic kidney, heart or skin grafts. The difficulties encountered in the clinical situation to obtain tolerance of small-bowel transplantation (SBT), in spite of massive non-specific immunosuppression, led us to study possible liver-induced tolerance in SBT. Inbred DA (RTIa) and PVG (RT1c) rats were used respectively as donors and recipients and divided in two groups: group 1: SIT alone (n = 6); group 2: combined OLT/SBT (n = 6). SIT was performed 17 days after OLT. No immunosuppressive treatment was given to the recipients. Biopsies of small-bowel grafts were performed in both groups at various times after small bowel engraftment. All animals in group 1 showed evidence of acute rejection of the graft between days 6 and 9 post-graft. The histologic pattern of rejection associated lamina propria (LP) mononuclear cell infiltration, crypt lesions and villous atrophy at the end-point of rejection. In group 2, long-term survival (> 100 days) of small bowel grafts was achieved in five of the six animals in spite of strong mononuclear cell infiltration in the LP, which peaked two months after small bowel grafting but then disappeared partially. This striking mononuclear cell infiltrate contrasted with only minor epithelial damage. These data demonstrate that liver grafting can enhance the survival of a small-bowel graft from the same donor in a rat model. Histological findings show that an intense immunological reaction takes place within liver-induced tolerated small-bowel grafts.