Liver transplantation in the rat. Biochemical and histological evidence of complete tolerance induction in non-rejector strains

Abstract

Orthotopic liver allografts in the rat survive indefinitely without immunosuppressive agents, despite incompatibility between donor and recipient for antigens of the major histocompatibility complex. This is strain-dependent. In the DA to PVG strain combination, liver grafts are never rejected. This is not due to failure of the recipient to mount an immune response against the donor tissue, because there is unequivocal histological evidence of a rejection response during the first few weeks after grafting. This response is moderate and disappears to leave a histologically normal liver, apart from mild bile duct proliferation. Liver function tests show evidence of damage during the phase of cellular infiltration, but these test results also return to normal levels within a few weeks. In the DA to BN strain combination liver grafts are rapidly rejected, and this process is accompanied by histological signs of a violent and progressive destructive cellular response with gross alterations in liver function test results that are progressive until the death of the recipients. F1 hybrid recipients between these two strains (BN X PVG)F1 show intermediate levels of both histological damage and elevated liver function values, but they do not reject their grafts. Recovery from the rejection episode appears to be complete, as judged histologically. However, biochemical values remain slightly elevated, indicating either that the original damage was so severe that it was inconsistent with complete functional recovery or that there is continuous damage that is not visible histologically.