Modification of the Immune Response by Oral Tolerance: Antigen Requirements and Interaction with Immunogenic Stimuli

The present study was undertaken to define requirements for antigen in induction and maintenance of oral tolerance and to evaluate the interrelationship between simultaneously administered oral tolerogenic and parenteral immunogenic stimuli. Tolerance was induced by a single gastric intubation of OVA and was assessed by absence of OVA-specific T lymphocyte proliferation in vitro. Tolerance was short termed and held for 21 days in the absence of additional antigen; alternatively, antigen persistence enabled prolonged maintenance of tolerance. Since tolerogenic and immunogenic stimuli reflect two distinct pathways of the immune system, we investigated the consequences of their simultaneous administration. When tolerogenic stimuli preceded immunogenic stimuli up to a minimal period of 24 hr, unresponsiveness dominated. Furthermore, tolerogenic stimuli were able to reduce the level of T lymphocyte proliferation when administered at the time of, and after, immunization. The degree of reduction was inversely related to the interval between parenteral immunization and gastric intubation. Repeated tolerogenic stimuli caused a further substantial reduction in residual T lymphocyte responses. These findings indicate that prevalence of tolerance in the immune response requires rapid dissemination and long term persistence of antigen.