Yokoi H, Kato K, Kezuka T, Sakai J, Usui M, Yagita H, Okumura K
Department of Ophthalmology, Tokyo Medical College Hospital, Japan.
Eur J Immunol. 1997 Mar;27(3):641-6. doi: 10.1002/eji.1830270310.
Experimental autoimmune uveoretinitis (EAU) induced by immunization with interphotoreceptor retinoid-binding protein (IRBP), a retinal self antigen, has been regarded to be a typical T helper type 1 (Th1)-mediated inflammatory disease. In this study, we examined the effect of a neutralizing monoclonal antibody (mAb) to interleukin-12 (IL-12), which has been known to play a critical role in the Th1 differentiation, on the development of EAU. While 9 of 13 control mice developed EAU by the immunization with IRBP, none of 12 mice developed EAU when given anti-IL-12 mAb 1 day before immunization. These mice did not develop EAU even after a rechallenge with IRBP on day 30, indicating that a protective mechanism had been established by the anti-IL-12 treatment. The proliferative response of splenocytes to IRBP in vitro was not significantly impaired, but the production of IL-2 and IFN-gamma was greatly reduced by the anti-IL-12 treatment. Moreover, production of IL-5 and expression of IL-4 mRNA were increased by the anti-IL-12 treatment. Consistently, IgG2a anti-IRBP serum antibodies were decreased and IgG1 were increased. Administration of a neutralizing anti-IL-4 mAb at the time of IRBP rechallenge reversed the protection established by the anti-IL-12 treatment at the primary immunization. These results indicate that the anti-IL-12 treatment at the IRBP priming not only prevented the development of pathogenic Th1 cells, but also induced suppressive Th2 cells that protect the animals from further challenge with the same antigen.
用视网膜自身抗原光感受器间维生素A结合蛋白（IRBP）免疫诱导的实验性自身免疫性葡萄膜视网膜炎（EAU）被认为是一种典型的1型辅助性T细胞（Th1）介导的炎症性疾病。在本研究中，我们检测了一种已知在Th1分化中起关键作用的白细胞介素12（IL-12）中和单克隆抗体（mAb）对EAU发病的影响。虽然13只对照小鼠中有9只通过IRBP免疫患上了EAU，但12只小鼠在免疫前1天给予抗IL-12 mAb后均未患上EAU。这些小鼠即使在第30天用IRBP再次攻击后也未患上EAU，这表明抗IL-12治疗已建立了一种保护机制。体外脾细胞对IRBP的增殖反应未受到明显损害，但抗IL-12治疗使IL-2和干扰素-γ的产生大大减少。此外，抗IL-12治疗使IL-5的产生和IL-4 mRNA的表达增加。一致地，IgG2a抗IRBP血清抗体减少，而IgG1增加。在IRBP再次攻击时给予中和性抗IL-4 mAb可逆转抗IL-12治疗在初次免疫时建立的保护作用。这些结果表明，在IRBP启动时进行抗IL-12治疗不仅可预防致病性Th1细胞的发育，还可诱导抑制性Th2细胞，从而保护动物免受相同抗原的进一步攻击。
