Hirose S
Department of Ophthalmology, Hokkaido University School of Medicine, Sapporo, Japan.
Hokkaido Igaku Zasshi. 1990 Nov;65(6):604-11.
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.
已有报道称不同品系大鼠对实验性自身免疫性葡萄膜炎(EAU)的易感性存在差异。本研究旨在区分主要组织相容性抗原复合体(MHC)基因和非MHC基因对EAU发病的影响。通过用牛视网膜S抗原(S-Ag)或肽M(一种与牛S-Ag第303至320位相对应的合成多肽)免疫,检测EAU易感的LEW大鼠、EAU抗性的WKAH大鼠、具有WKAH遗传背景且代表LEW MHC的1L MHC同源系大鼠以及其他9种近交系大鼠发生EAU的能力。我们发现只有LEW大鼠发生了S-Ag诱导的EAU,而WKAH大鼠、1L同源系大鼠和其他大鼠未发生。然而,当额外注射百日咳博德特氏菌(BP)时,所有品系大鼠均发生了S-Ag诱导的EAU。相反,只有在RT1 II类亚区具有单倍型1的LEW、WKAH、1L、F344和NIG-III大鼠通过肽M和BP免疫发生了EAU。本研究结果表明,大鼠对EAU的易感性受MHC基因和非MHC基因共同控制。大鼠EAU的最终发病受非MHC基因控制。然而,当额外注射BP时,这种非MHC基因的作用不再能观察到。MHC II类(RT1[1]限制了对肽M诱导的EAU的易感性。然而,当使用多决定簇S-Ag作为免疫原时,未观察到这种MHC限制。