IMMUNOLOGICAL CONSEQUENCES OF INTERVENTION IN ESTABLISHED IMMUNE-RESPONSES BY FEEDING PROTEIN ANTIGENS

The usual result of feeding protein antigens to naive animals is the i nduction of profound immunological unresponsiveness and this is curren tly being exploited to treat inflammatory disease. Because the most us eful therapeutic application of feeding antigen would be to suppress e stablished disease, the aim of this study was to compare the immunolog ical basis of oral tolerance induced by feeding a model antigen to nai ve and primed animals. We show that feeding 2-200 mg ovalbumin (OVA) t o mice 7 days after immunisation with OVA in adjuvant produces dose-de pendent suppression of delayed-type hypersensitivity (DTH), T cell pro liferation, and both T(H)1 and T(H)2 cytokines, although serum IgG; le vels were unaffected. Feeding OVA before immunisation suppressed all t hese responses. Although feeding up to 8 days after immunisation could suppress some subsequent responses, tolerance was induced much more e ffectively when antigen was fed in the first 4 days after immunisation . Tolerance in primed mice was intact in IL-4(-/-)mice, indicating tha t it was not caused by selective upregulation of T(H)2 cells in vivo. We conclude that oral administration of protein antigen can inhibit on going responses by all effector T cell subsets, but the exact conseque nces, and therefore possibly the mechanisms, are different from those induced by tolerising naive mice. These findings may have important im plications for designing therapeutic regimes exploiting oral tolerance , (C) 1998 Academic Press.