Department of Ophthalmology, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Exp Eye Res. 2009 Oct;89(4):486-93. doi: 10.1016/j.exer.2009.05.009. Epub 2009 Jun 11.
Endogenous uveitis is a common cause of visual disability and blindness. The etiology of uveitis remains largely unknown but reasonable etiologic factors include infections. Superantigens are regarded as one of the leading causes of infectious etiology in autoimmune disease. However, the role of superantigens in uveitis remains unclear. In the present study, we investigated the effect of Staphylococcal enterotoxin B (SEB), a member of the superantigens, using an experimental model of autoimmune uveoretinitis (EAU). C57BL/6 mice were immunized with human interphotoreceptor retinoid binding protein (IRBP) peptide, and the severity of EAU disease was scored. Vehicle (PBS) alone or SEB dissolved in PBS was administered by intravenous injection on post-immunization day 10 or on post-immunization day 24. In addition, a systemic immune response study was performed to address the effects of SEB on systemic immunity. EAU was aggravated significantly by the injection of SEB at post-immunization day 10. Furthermore, relapse was induced by the injection of SEB at day 24. On the other hand, SEB injection without IRBP peptide immunization elicited no inflammatory changes in the uvea or retina. Furthermore, SEB enhanced not only the IRBP-specific T-cell proliferative responses but also IFN-gamma and IL-17 production. Moreover, the intraocular expression levels of these cytokines was also enhanced by SEB injection. Both anti-CD4 and -Vbeta8 Ab administration suppressed disease aggravation and the enhancement of IRBP-specific T-cell responses caused by SEB. These results suggest that SEB is involved significantly in the aggravation or recurrence of endogenous uveitis through activation of autoreactive uveitogenic T cells.
内源性葡萄膜炎是视力障碍和失明的常见原因。葡萄膜炎的病因在很大程度上仍然未知,但合理的病因包括感染。超抗原被认为是自身免疫性疾病感染病因的主要原因之一。然而,超抗原在葡萄膜炎中的作用尚不清楚。在本研究中,我们使用自身免疫性葡萄膜炎(EAU)的实验模型研究了葡萄球菌肠毒素 B(SEB)的作用,一种超抗原。C57BL/6 小鼠用人类视黄醇结合蛋白(IRBP)肽免疫,对 EAU 疾病的严重程度进行评分。单独用载体(PBS)或溶解在 PBS 中的 SEB 在免疫后第 10 天或第 24 天经静脉注射给药。此外,进行了系统免疫反应研究,以解决 SEB 对系统免疫的影响。在免疫后第 10 天注射 SEB 显著加重 EAU。此外,在第 24 天注射 SEB 可诱导复发。另一方面,在没有 IRBP 肽免疫的情况下注射 SEB 不会引起葡萄膜或视网膜的炎症变化。此外,SEB 不仅增强了 IRBP 特异性 T 细胞增殖反应,还增强了 IFN-γ和 IL-17 的产生。此外,SEB 注射还增强了这些细胞因子的眼内表达水平。抗 CD4 和 -Vbeta8 Ab 给药抑制了 SEB 引起的疾病加重和 IRBP 特异性 T 细胞反应的增强。这些结果表明,SEB 通过激活自身反应性致葡萄膜炎 T 细胞,显著参与内源性葡萄膜炎的加重或复发。