Establishment of an Acute Graft-Versus-Host Disease Model Following Liver Transplantation in Donor-Dominant One-Way Major Histocompatibility Complex Matching Rats

Abstract

Acute graft-versus-host disease is an uncommon but devastating complication following liver transplantation (LTx-aGVHD). We investigated whether a rat model of LTx-aGVHD could be established using Lewis rat donors and (LewisXBN)F1 rats as recipients, which provides favorable conditions for studies of graft-versus-host reaction or disease. Replacement of (LewisXBN)F1 livers by Lewis livers alone was not sufficient to induce aGVHD; all recipients grew in a normal pattern as the syngeneic liver transplantation (LT) from Lewis to Lewis rat. However, when various numbers of donor splenocytes (1 × 10 8, 2 × 10 8, 3 × 10 8, 4 × 10 8) were transferred simultaneously with the LT, the morbidities of lethal aGVHD were 16.7%, 50%, 83.3%, and 100%, respectively. The clinical courses as well as histologic analyses of skin and colon showed typical aGVHD characteristics. However, unlike transfusion-associated aGVHD, the liver graft was not involved. These clinical and histologic characteristics of aGVHD were consistent with those in humans who develop aGVHD after LT. Thus, a reproducible rat model of LTx-aGVHD was developed by performing LT from Lewis to (LewisXBN)F1 rats in combination with donor splenocyte transfusion. This model may be useful for further studies on the mechanisms and effective treatment modalities for LTx-aGVHD.