The induction of tolerance to a soluble protein antigen by oral administration.

The repeated administration of bovine serum albumin by stomach tube to Charles River and Black Norwegian rats resulted in a state of partial tolerance to the antigen. A very small amount of antibody was detected in the serum at the end of the oral regime but anti-BSA-producing cells could not be demonstrated in the lamina propria, in the Peyer's patches of the small intestine, in the mesenteric nodes or in the spleen of these animals. Antibody was not demonstrated in the small intestinal contents or in the faeces of the same animals. The antigen was absorbed in the native form and not as constituent peptides bearing antigenic determinants in common with the native protein. Preliminary data, using a radioimmunoassay, indicate that the serum concentration of BSA after the administration of 25 mg of the protein by stomach tube, is in the range 1-10 ng/ml of serum. Preliminary experiments indicate that the state of partial tolerance could not be abrogated by syngeneic spleen cells or peritoneal exudate cells from normal rats. This form of tolerance therefore has some features in common with the state of tolerance induced by the parenteral administration of small amounts of bovine albumin (low zone tolerance).