The immune response in cirrhotic rats. The induction of tolerance to orally administered protein antigens.

Hepatic cirrhosis reduced the susceptibility of rats to the induction of tolerance by the oral administration of a protein antigen. Rats with portacaval shunt were rendered tolerant as readily as normal rats. The orally induced state of partial tolerance was shown to be dependent on thymus-dependent lymphocytes: B lymphocytes reacted normally to challenge when injected with T lymphocytes from normal rats. Several factors may contribute to the reduced responsiveness of the cirrhotic rats to the tolerance regime. First, the cirrhotic liver was shown to have a reduced capacity to separate immunogen from tolerogen. Second, because of the reduced phagocytic capacity of the liver, increased quantities of lipopolysaccharide, derived from intestinal microorganisms, enter the blood stream. These substances and products of hepatocyte necrosis have adjuvant activity and may therefore contribute to the changed state of responsiveness of rats with cirrhosis.