The role of digestive enzymes in orally induced immune tolerance.

The influence of digestive enzymes on the tolerogenic properties of an orally administered protein antigen, Bovine Serum Albumin (BSA), in the mouse has been investigated. A non-immunogenic peptic digest of BSA was found to be immunosuppressive when administered orally or directly injected into the mouse ileum. In contrast, untreated BSA was tolerogenic when administered orally but immunogenic following ileal administration. As determined by precipitin analysis of the proteins recovered from mouse feces, orally administered BSA was thoroughly degraded by the digestive system while the degradation in the ileum was quite limited. We conclude that to acquire tolerogenic properties, an orally administered protein must be first degraded by the proteolytic enzymes of the gastrointestinal digestive system.