INDUCTION OF SYSTEMIC IMMUNOLOGICAL HYPORESPONSIVENESS TO OVALBUMIN IN NEONATAL RATS BY THE ENTERIC ADMINISTRATION OF PEPTIC FRAGMENTS OF OVALBUMIN

The orogastric administration of protein antigens can induce specific systemic immunologic hyporesponsiveness to the antigens. Some evidence has suggested that fragmentation of the antigens by proteolytic enzymes in the gastrointestinal tract is a necessary step in this phenomenon. We administered either ovalbumin (OVA) or fragments of OVA, produced by digestion with pepsin, into the stomach or jejunum of suckling rats and measured the serum IgG antibody response to a subsequent intraperitoneal challenge with OVA. Whereas OVA administered by gastric gavage caused virtually a complete unresponsiveness to the OVA challenge, administration into the jejunum had no significant effect. Administration of peptic fragments of OVA (about 8000 Da) into either the jejunum or stomach caused systemic unresponsiveness in 62 % and 67 % of animals, respectively (p < .05 vs buffer-fed controls). Smaller fragments of OVA (<2000 Da) given into the stomach or jejunum had no effect on systemic IgG responses, nor did administration of the 8000 Da fragments intraperitoneally. We conclude the 1) systemic immunologic tolerance to OVA can be induced by enteric administration of critical-size fragments of OVA, and 2) encounter of the OVA fragments, like intact OVA, via the gut yields a distinctly different response from that which follows parenteral administration.