Histopathology of bile ducts in F1 rats hybridized from parents with different major histocompatibility antigens, undergoing inoculation with maternal strain lymphocytes during the fetal period

Abstract

In 1979, Seemayer suggested that biliary atresia (BA) might represent maternal or postnatally induced graft-versus-host reactions in which the liver is the principal target for aggressor lymphocytes. We attempted to produce perinatal graft-versus-host disease (GVHD) models to clarify the causal relationship between BA and GVHD. F1 rats were hybridized from parents with different major histocompatibility antigens: inbred strain maternal Lewis (LEW) and paternal Brown Norway (BN). F1 hybrid rats between 16 and 18 days' gestational age (term: 21 days) were given a single intrahepatic inoculation of mixed lymphocytes (1 × 10⁷/ml) from spleen and peripheral blood of female LEW rats. Forty-seven (25.6%) of 184 F1 hybrid rats receiving lymphocyte inoculation were born alive. They were killed immediately after birth or between 1 and 65 days of age for histologic examination. Abnormalities of the intrahepatic bile ducts were noted in 16 (84.2%) of 19 rats, while 3 (60%) of 5 showed abnormalities of the extrahepatic bile ducts. Main histological features involved periductal lymphoid cell infiltration and intraepithelial lymphoid cell invasion as well as epithelial degeneration. The histologic changes corresponded to those in GVHD, and furthermore showed common findings observed in BA.