Immune status in mice with experimental biliary obstruction

Abstract

Obstructive jaundice was induced in mice by common bile duct ligation (CBDL). High levels of total blood bilirubin (12.7 ± 1.5 mg/100 ml) were observed after 10–20 days of obstruction and 15.8 ± 2.3 mg/100 ml after 1–2 months. The spleen indices in the CBDL mice were significantly elevated, whereas the thymus weights and content of lymphoid cell in thymus were drastically reduced. Immunization of biliary-obstructed mice with a thymus-dependent antigen, sheep red blood cells (SRBC), exhibited a markedly suppressed direct plaque-forming and rosette-forming cell response, although there was no significant difference in serum hemagglutinin titers after second immunization with SRBC. The primary plaque-forming response of CBDL mice against a thymus-independent antigen, Escherichia coli lipopolysaccharide, was threefold higher in magnitude than controls. The mean survival time of skin allografts in CBDL mice was prolonged. On the other hand, splenic lymphoid cells isolated from biliary-obstructed mice and injected in allogeneic newborn recipients gave equal magnitude of graft versus host reaction as control cells. Incubation of normal lymphocytes with bilirubinemic serum caused nonspecific blastogenesis of the cells. The results presented here indicate that biliary obstruction alters the normal immune pattern. It is suggested that severe bilirubinemia leads to disruption of the balance of cell subpopulation reactivity leading to blocked T-cell function. This impaired function is reflected in depressed graft rejection, reduced primary response to thymus-dependent antigen, and greater response to a thymus-independent antigen. Possible explanations of the mechanism(s) involved are suggested.