S-antigen. Experimental autoimmune uveitis following immunization with a small synthetic peptide

Experimental autoimmune uveitis was observed following the immunization of Lewis rats with a small synthetic peptide, peptide M (18 amino acids in length), which corresponds to the amino acid sequence of a well-characterized region of S-antigen (404 amino acids in length). Rats were immunized with varying doses of peptide M ranging from 1 to 100 micrograms in complete Freund's adjuvant. As little as 5 micrograms of the synthetic peptide was sufficient for the induction of disease. Clinically, the disease that developed was characterized by iris and pericorneal hyperemia followed by exudates in the anterior chamber. Histopathologically, a severe inflammatory response was observed in animals immunized with high doses of the peptide (greater than 50 micrograms). In these eyes the photoreceptor cell layer of the retina was completely destroyed. A massive subretinal exudate containing mononuclear cells and polymorphonuclear leukocytes was also present. The inflammatory changes were generally less severe following immunization with low doses of the peptide (less than 50 micrograms), and in some eyes only occasional focal lesions were observed. In addition, animals with ocular inflammatory disease had associated pinealitis characterized by a lymphocytic infiltration of the subcapsular and central area of the pineal gland. Both clinically and histopathologically, the experimental autoimmune uveitis produced by the synthetic peptide was indistinguishable from the disease caused by native S-antigen. We comment on the significance of these findings and the relationship of S-antigen in the pathogenesis of experimental autoimmune uveitis.