Caspi R R, Chan C C, Leake W C, Higuchi M, Wiggert B, Chader G J
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892.
J Autoimmun. 1990 Jun;3(3):237-46. doi: 10.1016/0896-8411(90)90143-g.
Experimental autoimmune uveoretinitis (EAU) in the mouse is a recently developed model of ocular autoimmunity. Dependence of disease induction on qualitative and quantitative parameters of immunization was studied in B10.A mice immunized with interphotoreceptor retinoid-binding protein (IRBP). It was found that use of Bordetella pertussis adjuvant as well as its mode of preparation was of critical importance for disease induction; no disease was induced if pertussis adjuvant was omitted. The minimal effective protocol for EAU induction when the vaccine form of B. pertussis adjuvant was used consisted of pretreatment with cyclophosphamide, two divided doses of IRBP in complete Freund's adjuvant (CFA), and two divided doses of B. pertussis vaccine. Any reduction in the immunization schedule resulted in reduced incidence of disease. In contrast, substituting purified B. pertussis toxin (PTX) for the vaccine allowed reduction of the immunization schedule to a single dose of IRBP in CFA and omission of the cyclophosphamide pretreatment. Severity and incidence of disease could be quantitatively controlled by varying the respective doses of IRBP and PTX. In addition, a chronic or an acute clinical course of EAU could be obtained by using either a low-dose or a high-dose immunization, respectively. Establishment of a single dose induction protocol and the quantitation of the immunopathogenic response as a function of the variables of immunization lay the foundation for the further development and utilization of this promising model of ocular autoimmunity.
小鼠实验性自身免疫性葡萄膜视网膜炎（EAU）是一种最近建立的眼部自身免疫模型。在以光感受器间维生素A结合蛋白（IRBP）免疫的B10.A小鼠中，研究了疾病诱导对免疫定性和定量参数的依赖性。结果发现，使用百日咳博德特氏菌佐剂及其制备方式对疾病诱导至关重要；若省略百日咳佐剂，则不会诱导出疾病。当使用百日咳博德特氏菌佐剂的疫苗形式时，诱导EAU的最小有效方案包括用环磷酰胺预处理、在完全弗氏佐剂（CFA）中分两次注射IRBP以及分两次注射百日咳博德特氏菌疫苗。免疫方案的任何减少都会导致疾病发病率降低。相比之下，用纯化的百日咳博德特氏菌毒素（PTX）替代疫苗可将免疫方案减少至在CFA中单次注射IRBP，并省略环磷酰胺预处理。通过改变IRBP和PTX的各自剂量，可以定量控制疾病的严重程度和发病率。此外，分别使用低剂量或高剂量免疫可获得EAU的慢性或急性临床病程。建立单剂量诱导方案以及根据免疫变量对免疫致病反应进行定量，为进一步开发和利用这种有前景的眼部自身免疫模型奠定了基础。
