Failure to induce oral tolerance to protein antigens in neonatal mice can be corrected by transfer of adult spleen cells.

We have examined the mechanisms that prevent the induction of oral tolerance to protein antigens in neonatal mice. Serum collected from adult mice 1 h after feeding ovalbumin (1 mg/g body wt) was adoptively transferred to mice aged 1, 3, and 42 d (40 microL/g body wt). Whereas delayed-type hypersensitivity was significantly suppressed in adult recipients relative to control groups, no suppression of systemic delayed-type hypersensitivity was found in neonatal recipients. In attempts to identify the immunologic deficiency that prevents mature reactivity to protein antigens in neonates, adult splenocytes were transferred intraperitoneally (10(8) cells/recipient) 24 h before a feed of OVA (1 mg/g body wt) to neonates. Significant suppression of their systemic DTH response, but not of their anti-ovalbumin IgG antibody response was observed, indicating that spleen cell transfer only partially confers adult-type reactivity. Similar results were obtained using a second protein antigen, BSA. Our observations suggest that the failure to induce oral tolerance to protein antigens in neonatal mice is not simply due to immature antigen processing by the gut, but probably reflects cellular and/or antigen handling immaturity of the neonatal immune system.