Hirose S, Ogasawara K, Natori T, Sasamoto Y, Ohno S, Matsuda H, Onoé K
Department of Ophthalmology, School of Medicine, Hokkaido University, Sapporo, Japan.
Clin Exp Immunol. 1991 Dec;86(3):419-25. doi: 10.1111/j.1365-2249.1991.tb02947.x.
Experimental autoimmune uveitis (EAU) is an organ-specific autoimmune disease and has served as a model of certain ocular inflammatory conditions in man. The present study was aimed at separating the effects of MHC and non-MHC genes on the development of EAU in the rat. EAU-susceptible LEW (RT1l), EAU-resistant WKAH (RT1k), and WKAH.1L (RT1l) MHC congenic strain of WKAH background rats were immunized with retinal soluble antigen (S-Ag) in Freund's complete adjuvant (FCA). LEW rats showed typical EAU, while neither WKAH nor WKAH.1L congenic rats developed EAU. However, when an additional i.v. injection of Bordetella pertussis was given, all rat strains developed EAU. Furthermore, when immunized with peptide M, an 18-mer synthetic peptide, which corresponds to amino acid positions 303-320 of bovine S-Ag, and given an additional i.v. injection of B. pertussis, LEW and WKAH.1L rats developed EAU, whereas WKAH did not. When ACI (RT1avl), BUF (RT1b), LEJ (RT1j), W (RT1k), F344 (RT1lvl), BN (RT1n), NIG-III (RT1q), TO (RT1t), and SDJ (RT1u) rats were immunized with peptide M or S-Ag and then B. pertussis, all strains developed EAU by immunization with S-Ag plus B. pertussis, but only F344 and NIG-III developed EAU by immunization with peptide M. These findings suggest that susceptibility to EAU in rats is controlled by both MHC and non-MHC genes; and that in the absence of B. pertussis adjuvant, the form of disease induced by native S-Ag in FCA is governed by non-MHC gene(s). However, this effect of non-MHC gene(s) could no longer be observed when the rats were also injected with B. pertussis adjuvant at sensitization.
实验性自身免疫性葡萄膜炎（EAU）是一种器官特异性自身免疫性疾病，已被用作人类某些眼部炎症性疾病的模型。本研究旨在区分主要组织相容性复合体（MHC）基因和非MHC基因对大鼠EAU发病的影响。将EAU易感的LEW（RT1l）、EAU抗性的WKAH（RT1k）以及WKAH背景大鼠的WKAH.1L（RT1l）MHC同基因品系用视网膜可溶性抗原（S-Ag）与弗氏完全佐剂（FCA）一起免疫。LEW大鼠表现出典型的EAU，而WKAH和WKAH.1L同基因大鼠均未发生EAU。然而，当额外静脉注射百日咳博德特氏菌时，所有大鼠品系均发生了EAU。此外，用对应于牛S-Ag第303 - 320位氨基酸的18聚体合成肽M免疫，然后额外静脉注射百日咳博德特氏菌时，LEW和WKAH.1L大鼠发生了EAU，而WKAH未发生。当用肽M或S-Ag免疫ACI（RT1avl）、BUF（RT1b）、LEJ（RT1j）、W（RT1k）、F344（RT1lvl）、BN（RT1n）、NIG-III（RT1q）、TO（RT1t）和SDJ（RT1u）大鼠，然后注射百日咳博德特氏菌时，所有品系通过用S-Ag加百日咳博德特氏菌免疫均发生了EAU，但只有F344和NIG-III通过用肽M免疫发生了EAU。这些发现表明，大鼠对EAU的易感性由MHC基因和非MHC基因共同控制；并且在没有百日咳博德特氏菌佐剂的情况下，FCA中天然S-Ag诱导的疾病形式由非MHC基因控制。然而，当在致敏时给大鼠也注射百日咳博德特氏菌佐剂时，这种非MHC基因的作用就不再能观察到了。
