Tolerance of islet allografts induced by orthotopic liver transplantation

Background. The induction of immunological tolerance by orthotopic liver tr ansplantation (OLT) is donor-specific. Moreover, after the acceptance of a liver, other organs are not rejected. The aim of this study is to clarify c haracteristics of the prolonged islet survival as a result of immunological tolerance which was induced following simultaneous OLT. Materials and methods. About 2000 islets were isolated from F344 rats. OLT was performed from F344 rats to diabetic LEW rats. Then the islets were tra nsplanted into the transplanted F344 livers of diabetic LEW rats. Survival of the pancreatic islet allografts and deposits of IgM and IgG; in the tran splanted liver and islets were investigated. Results. Survival time in the group with OLT (mean survival time: 46.4 +/- 38.2 days) was significantly longer than that without OLT (mean survival ti me: 8.1 +/- 0.8 days) (P < 0.01). Amount of serum antibody against donor ly mphocytes was slightly higher in the group without OLT, and was very high i n the group with OLT. Histologically, severe lymphocytic infiltration was o bserved in the Glisson's sheaths in the group with OLT. Islets were lodged, without lymphocytes inside, in small branches of the portal vein 7 days af ter transplantation. Immunohistologically, IgM and IgG deposits were found in the Glisson's sheaths and along sinusoids; however, they were not found in the islets. Conclusions. Induction of immunological tolerance and long-term survival of islets are possible by simultaneous OLT. The mechanism of this tolerance c ould be the host's selection of the liver as a target of preferred immunolo gical attack. (C) 1999 Academic Press.