Genetic control of susceptibility to experimental autoimmune uveoretinitis in the mouse model: Concomitant regulation by MHC and non-MHC genes

Understanding Autoimmune Uveitis through Animal Models The Friedenwald Lecture

“…Thus, the C57Black background (B10 or B6) is permissive to EAU expression, provided that there is a susceptible H-2 haplotype such as H-2 r , H-2 k (or the closely related H-2 a ) or H-2 b , in that order of susceptibility. 15 The study of human MHC molecules in susceptibility was made possible by adaptation of the EAU model to "humanized" mice, which are HLA-transgenic strains in which mouse MHC molecules have been replaced by human MHC molecules. We showed that several human HLA class II molecules support EAU development in response to S-Ag, which is the main antigen recognized by lymphocytes of uveitis patients, but to which wild-type parental mouse strains are resistant.…”

Mesenchymal Stem Cells Induce Functionally Active T-Regulatory Lymphocytes in a Paracrine Fashion and Ameliorate Experimental Autoimmune Uveitis

“…It represents autoimmune uveitis in humans, which is a group of diseases affecting the eye and estimated to be responsible for 10% of the cases of severe visual handicap that show associations with major histocompatibility complex (MHC) class I or class II molecules, 15 and MHC-restricted presentation of uveitogenic antigens has been demonstrated to be a key event in the pathogenesis of uveitis in humans 16 and in animal models. 17 As in clinical uveitis, susceptibility to EAU is genetically controlled, and the responsiveness to EAU induction is determined by the effect of genes belonging to the MHC, H2 in mouse, and other non-MHC genes. 15 MHC gene control is determined largely by epitope recognition, and in mouse some H2 haplotypes, if present on the appropriate background, are conducive to disease induction.…”

Central Tolerance Mechanisms in Control of Susceptibility to Autoimmune Uveitic Disease

“…In addition, BALB=c and AKR=J mice, which are also resistant to IRBP-induced disease [23], expressed IRBP in their thymus. On the other hand, no IRBP mRNA was detected in B10.A and B10.RIII, two strains susceptible to IRBP-induced disease [27]. These results are also summarized in Table 1.…”

“…Figure 1 shows results of a published study [23] in which four inbred strains of mice were examined for thymic expression of arrestin or IRBP. All four strains are resistant to arrestininduced EAU [27] and were found to express arrestin mRNA in their thymi. In addition, BALB=c and AKR=J mice, which are also resistant to IRBP-induced disease [23], expressed IRBP in their thymus.…”

“…More recently, a correlation has been noted between susceptibility to experimental autoimmune encephalomyelitis and the absence of the target peptide in thymi of mice susceptible to this disease [36À38]. a Susceptibility of EAU of mice is recorded in [27] and of rats in [29]. b Disease or mRNA transcript observed in a small portion of tested animals.…”