Thymic expression of autoantigens correlates with resistance to autoimmune disease

Experimental autoimmune uveoretinitis (EAU), an animal model for human intraocular inflammation (uveitis), is induced by immunization with retinal proteins such as S-Ag or interphotoreceptor retinoid binding protein. Marked differences exist among different animal species and strains in their susceptibility to EAU induction, but the cause of these differences is not completely clear. Here we show for the first time a correlation between constitutive expression of ocular autoantigens in the thymus (mRNA and protein) and resistance to EAU. This correlation was noted both at the species (mice vs rats or monkeys) and the subspecies (differences among strains) level. The data thus provide a novel mechanistic explanation for the differences in susceptibility to autoimmune diseases, suggesting that resistance to an organ-specific autoimmune disease may be regulated at least in part by capacity to establish central tolerance to the relevant autoantigen.