Immunologic outcome of enteric administration of ovalbumin to neonatal rats is anatomic-site specific

An important immunologic response to the oral ingestion of a protein antigen is systemic tolerance to subsequent parenteral encounter with the same antigen. In the newborn intestine, ileal epithelial cells nonspecifically take up macromolecules and degrade them in lysosomal enzyme-containing vacuoles. We speculated that processing of protein antigens by the ileal cells helps mediate systemic immunologic tolerance to the antigens. Therefore, we developed a neonatal rat model in which ovalbumin (OVA) was administered either by gastric gavage or by infusion into surgically constructed loops of jejunum or ileum. We also administered OVA to other groups of animals by injection into the intact jejunum or ileum. Two and 4 weeks later, animals were challenged with OVA measured. Whereas animals that received OVA by gastric gavage were made tolerant to the protein (produced no detectable serum IgG anti-OVA antibodies after parenteral challenge), the animals given OVA into the jejunum or ileum did not show tolerance; indeed, some of those given OVA into the ileum were immunized by the enteric exposure. From these data we postulate that the development of systemic immunologic tolerance to a protein antigen in the newborn requires "upstream" processing of the antigen by gastric or pancreatic secretions and that exposure of the distal intestine to intact protein antigens can result in systemic sensitization to the antigens. The latter response might be causally linked to food allergies or autoimmune diseases.