Immunological responses to fed protein antigens in mice. II. Oral tolerance for CMI is due to activation of cyclophosphamide-sensitive cells by gut-processed antigen.

Mice fed ovalbumin develop specific systemic hyporesponsiveness. This oral tolerance is abrogated by cyclophosphamide pretreatment, and the mechanism of abrogation could be either via T suppressor cells or via damage to the gut epithelium. A serum transfer protocol was used to examine the site of action of cyclophosphamide in this system. Serum was collected from ovalbumin-fed mice and transferred into recipients which were then parenterally immunized with ovalbumin in Freund's complete adjuvant. Serum transfer suppressed the delayed-type hypersensitivity (DTH) responses but not the antibody responses of the recipients. Cyclophosphamide pretreatment (100 mg/kg) of recipients (but not of donors) abrogated this suppressor effect. Parenteral administration of ovalbumin in a range of doses did not induce immunological hyporesponsiveness. It is suggested that absorption across the gut mucosa leads to generation of fragments of ovalbumin that induce suppressor cells selective for DTH.