Single and multiple intragastric feedings of ovalbumin (OVA) to high-responder BDF1 mice resulted in virtually complete unresponsiveness to later parenteral immunization with OVA in Al(OH)3 adjuvant, as indicated by antibody titers in Farr assays and in passive cutaneous anaphylaxis (PCA) assays for IgE antibodies. Repeated feedings of partially tolerizing doses of antigen had a cumulative inhibitory effect on subsequent responsiveness. Slight increases in primary antigen binding were detected in the serum of antigen-fed mice not given parenteral immunization, although rates of clearance of radiolabeled OVA from the blood were similar in normal and tolerant animals. Serum recovered from tolerant mice 7 or 14 days after feeding did not inhibit antibody responses of normal recipients. Responsiveness of normal or OVA-primed syngeneic spleen cells was substantially reduced upon transfer into recipients that were previously fed OVA, when compared with transfer into saline-fed recipients. The differences in responsiveness of lymphocytes transferred into OVA- and saline-fed mice were completely eliminated by irradiation (850 R) of the recipient animals either 7 or 20 days after feeding and immediately before the transfer.
The results indicated that the state of tolerance after ingestion of OVA is actively maintained, but did not support the hypothesized mediation of this tolerance by orally induced antibodies or serum factors that have been associated with unresponsiveness to ingested antigens in similar experimental systems.
This work was supported in part by United States Public Health Service Grant AI 13474.