INTERPHOTORECEPTOR RETINOID-BINDING PROTEIN IS A POTENT TOLEROGEN IN LEWIS RAT - SUPPRESSION OF EXPERIMENTAL AUTOIMMUNE UVEORETINITIS IS RETINAL ANTIGEN-SPECIFIC

Aims-Administration of unfractionated retinal antigen(s) (retinal extr act, RE) suppresses RE induced experimental autoimmune uveoretinitis ( EAU) and offers a potential therapeutic alternative to nonspecific imm unosuppressive therapies for posterior uveitis and autoimmune diseases . S-Ag and interphotoreceptor retinoid binding protein (IRBP) are two major autoantigens within soluble RE. It was aimed to assess, firstly, as has previously been shown with S-Ag, if IRBP can induce intranasal tolerance and, secondly, the contribution of both these major autoant igens to tolerance induction by whole RE. Methods-Animals were toleris ed by intranasal administration with S-Ag or IRBP, either alone or in combination, or RE before immunisation with either IRBP or RE. Control animals were administered nasally either PBS or MBP. Daily clinical r esponses were recorded biomicroscopically and histological grades were obtained using a semiquantitative scoring system. Weekly serum antibo dy levels to retinal antigens were measured by ELISA and delayed hyper sensitivity responses (DTH) were assessed by skin reactivity to intrad ermal inoculation with retinal or non-specific antigens. Results-Micro gram doses of IRBP successfully suppressed both clinically and histolo gically IRBP induced EAU. This suppression was accompanied by reduced antigen specific DTH reactivity but maintained T cell dependent (IgG2a ) antibody responses. Furthermore, combined S-Ag and IRBP administrati on afforded equal suppression of RE induced EAU when compared with RE therapy alone. Suppression of RE induced EAU was not achieved with adm inistration of a nonretinal specific autoantigen, MBP. Although indivi dually, both S-Ag and IRBP suppressed RE induced EAU, whole RE was una ble to protect against IRBP induced disease. Conclusions-Intranasal ad ministration of IRBP suppressed IRBP induced EAU in the Lewis rat. S-A g and IRBP are the major contributors to the tolerogenicity within RE, despite the known uveogenicity of other retinal antigens within RE an d induction of tolerance was retinal antigen specific. Furthermore, su ppression induced by single antigen administration is antigen specific although concomitant bystander suppression may also play a role. RE w as unable to protect against IRBP induced disease despite tolerogenic levels of antigen within RE. Although this may be due in part to a dos e effect of either tolerising or immunising antigen, further investiga tion into the possible antigen dominance of IRBP or mucosal processing of combinations of antigens is necessary so that the full efficacy of mucosal tolerance therapy can be assessed.