[Genetic control of experimental autoimmune uveitis in rats]

Differences in susceptibility to experimental autoimmune uveitis (EAU) among rats of various strains have been reported. The present study was aimed at separating the effects of the major histocompatibility antigen complex (MHC) and non-MHC genes on the development of EAU. EAU-susceptible LEW, EAU-resistant WKAH, WKAH, 1L MHC congenic strain rats representing MHC of LEW on WKAH genetic background, and other nine inbred strains of rats were examined for their ability to develop EAU by immunization with bovine S-Ag or peptide M, an synthetic polypeptide corresponding to position 303 to 320 in bovine S-Ag. We found that only LEW rats developed S-Ag induced-EAU, where WKAH, 1L congenic and other rats did not. However, when an additional injection of Bordetella pertussis (BP) was given, all rat strains developed S-Ag induced-EAU. In contrast, only LEW, WKAH, 1L,F344, and NIG-III rats, which have haplotype 1 at RT1 class II subregions developed EAU by immunization with peptide M and BP. The present findings showed that the susceptibility to EAU in rats was controlled by both MHC and non-MHC genes. Eventual development of EAU in rats was governed by non-MHC gene (s). However, this effect of non-MHC gene (s) could no longer be observed when an additional injection of BP was administered. MHC class II (RT1(1] restricted the susceptibility to peptide M induced-EAU. However, this MHC restriction was not observed when multideterminant S-Ag was used as an immunogen.