Adjuvant activity of Escherichia coli heat-labile enterotoxin and effect on the induction of oral tolerance in mice to unrelated protein antigens

Abstract

The ability of Escherichia coli heat-labile enterotoxin (LT) to influence the induction and maintenance of tolerance was examined in animals primed orally with a soluble protein antigen, ovalbumin (OVA), or in animals primed orally with two unrelated protein antigens administered simultaneously, OVA and bovine serum albumin (BSA). LT is immunologically and structurally related to the cholera enterotoxin (CT), which has been shown to be capable of abrogating oral tolerance to protein antigens when delivered simultaneously with the antigens. In this study, simultaneous administration of LT with OVA was shown to prevent the induction of tolerance to OVA and to increase the serum anti-OVA IgG response 30- to 90-fold over OVA-primed and PBS-primed animals, respectively. This effect was determined to be a function of the enzymatically active A subunit of the toxin since the B (binding) subunit alone was unable to influence tolerance induction. Animals fed LT with OVA after the initial OVA prime developed a significantly lower serum IgG and mucosal IgA anti-OVA response than those fed LT with OVA in the initial immunization, indicating that prior exposure to the antigen reduces the effectiveness of LT to influence tolerance and its ability to act as an adjuvant. LT was not able to abrogate tolerance once it had been established. Serum IgG and mucosal IgA responses in animals receiving LT on only a single occasion, that being upon first exposure to antigen, were equivalent to responses after three OVA/LT primes, indicating that commitment to responsiveness occurs early and upon first exposure to antigen.(ABSTRACT TRUNCATED AT 250 WORDS)