Oral tolerance to ovalbumin in mice: induction and long-term persistence unaffected by Staphylococcus aureus enterotoxin B and Clostridium perfringens type A enterotoxin.

Abstract

Oral administration of dietary antigen (Ag) results in the systemic Ag-specific immunologic unresponsiveness termed oral tolerance. Its induction is of importance in the young where numerous symptoms are associated with IgE-mediated food-hypersensitivity reactions. Two related enterotoxins, cholera toxin and Escherichia coli heat-labile enterotoxin, have been shown to abrogate oral tolerance (i.e. IgG and IgE antibody (Ab) unresponsiveness) to an unrelated and simultaneously fed Ag. However, a critical role has been suggested for the gut flora in recovery of a hyporesponsive state. The purpose of the present study was to investigate whether the Staphylococcus aureus enterotoxin B (SEB) and Clostridium perfringens type A enterotoxin (CPE), involved in many diarrheas, could affect the induction and long-term persistence of oral tolerance to ovalbumin (OVA). Using conventional and germ-free mice fed once or twice with enterotoxin plus OVA, we investigated the possible role of the indigenous gut flora. In addition, we tested the influence of CPE synthesized in vivo in the digestive tract of gnotobiotic mice on the induction of OVA-specific oral tolerance. Mice were immunized intraperitoneally with OVA twice, and IgG and IgE Ab levels were measured by ELISA. Neither SEB nor CPE, orally given or synthesized in vivo (CPE), prevented the induction of oral tolerance to OVA. Moreover, the IgG Ab unresponsiveness persisted over 2 mo in the conventional mice fed with toxin plus OVA as also observed in the OVA controls. The results indicate that, independent of the gut flora's influence, SEB and CPE did not affect the induction nad long-term persistence of oral tolerance to co-ingested Ag.