Peptide-mediated suppression of experimental autoimmune uveoretinitis in mice: development of a peptide vaccine

Experimental autoimmune uveoretlnltls (EAU) Is an animal modelof antigen-specific, T_h cell-mediated, organ-specific autoimmunedisease. EAU is induced by immunization of B10.A mice with Interphotoreceptorretlnold-binding protein (IRBP). Pre-treatment with syntheticpeptlde 518–529 derived from IRBP prevented IRBP-medlatedEAU. This was accompanied by augmentation of the IRBP-speciflclgG1 antibody (T_h2) response and down-regulation of the IRBP-specfflclgG2a (T_h1) response. Consistent with this is the observationthat two of two T cell lines established from p518–529-primedmice produced T_h2-type cytokines (IL-4 and IL-10), whereas threeof three T cell lines obtained from IRBP-prlmed mice producedT_h1-type cytokines (IL-2 and IFN-). Together this suggests thepossibility that p518–529 priming causes a shift froma T_h1- to a T_h2-domlnated Immune response, thereby playing apivotal role In the prevention of IRBP-mediated EAU. Furthermore,co-transfer of cells from a CD4⁺ p518–529-specfflc T cellline prevented the development of EAU after adoptive transferof spleen cells from mice with EAU Into normal mice. These findingscontribute to our understanding of the mechanism of EAU, particularlywith respect to the down-regulation of T_h1-initiated Inflammation,and may prove valuable for designing a peptlde vaccine for EAUIn the future.