BoIdToward Mechanisms of Oral Tolerance as Therapy for Experimental Autoimmune Uveitis (EAU)

We studied a model of clinical autoimmune eye disease in the Lewis rat induced by S-Ag injection, mediated by CD4 T cells. We showed that preinjection feeding using S-Ag peptides protected rats from disease induced by the same peptide or by an alternate S-Ag peptide or even by the entire protein. This evidence of protection through a suppressive mechanism occurred at low feeding doses. Suppressive protection was transferred to naive rats via T cells. At high pre-injection feeding doses anergy/deletion played major roles since protection occurred only with the same peptide used to induce the disease, and protection was not transferable. We have now studied post-injection feeding regimens. In this setting, protection was dose-responsive, where 5x5mg doses of S-Ag peptide 343-362 inhibited EAU caused by itself (Img and 200ug feeds were less effective). S-Ag pepiide 270-289 and IRBP peptide R-16 did not protect from 343-induced disease at these doses. Similarly, 270-289 inhibited only EAU caused by itself. We take this as evidence for the importance of anergy/deletion in preventing inflammation just prior to disease onset, since only high doses of inducing peptide optimally prevented disease. 5mg doses of peptides inhibited antibody and lymphoproliferative responses to S-Ag. Our results suggest that prevention of EAU by antigen feeding immediately prior to disease onset operated through induction of unresponsiveness (not suppression).