Study of experimental autoimmune uveoretinitis

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This paper describes the spontaneous occurrence of an autoimmune uveoretinitis in nude (nu/nu) mice reconstituted when 4 weeks old by the grafting of rat embryonic thymus (TG nude). The uveoretinitis was characterized histologically by progressive loss of the photoreceptor layer, observed in 4.0, 17.6, 42.9 and 71.4 percent of such mice at 3, 5, 7 and 12 months of age, respectively. Mice with uveoretinitis were shown to have serum IgG antibody reactive by indirect immunofluorescence with retinal photoreceptors, and with interphotoreceptor retinoid-binding protein (IRBP), but not retinal S-antigen, by immunoblotting and ELISA. IRBP is an approximately 140 kDa glycoprotein consisting of about 1260 amino acid residues. We found that residues 1182-1194 is the immunodominant determinant in TG nude mice, and that tryptophan at residue 1182 and proline at residue 1194 are agretopes of the peptide. A uveoretinitis could be adoptively transferred to syngeneic ungrafted nude mice by splenic CD4-positive T cells from diseased animals. This is the first experimental model of a (T-cell mediated) autoimmune uveoretinitis which develops spontaneously and which is not dependent upon deliberate sensitization with retinal antigens and adjuvants.