Oral Tolerance in Experimental Autoimmune Uveoretinitis: Feeding after Disease Induction Is Less Protective than Prefeeding

Abstract

Oral administration of antigen modulates subsequent immune responses raised by conventional subcutaneous priming. If experimental autoantigens are administered, subsequent induction of autoimmune diseases may be inhibited. However, feeding autoantigens after priming or disease induction is more clinically relevant, but the trials have been less successful. Using therapeutic feeding of peptides to inhibit experimental autoimmune uveoretinitis (EAU) induced in LEW rats by bovine S-Ag peptides, we found that only mild disease could be inhibited if feeding was delayed until after immunization, and relatively high feeding doses were required. In recipients with more severe EAU, the clinical efficacy of therapeutic feeding was minimal despite concurrent down-regulation ofin vitroantigen-specific lymphocyte proliferation and serum antibody responses. No further inhibition of EAU was found by increasing the feeding dose. Feeding the same peptides prior to immunization produced resistance to moderate to severe disease induction. Unlike prophylactic feeding protocols, conditions were found such that feeding after immunization with low doses of antigen led to worsening of mild disease, raising a note of caution.