重组IL-15/Fc融合蛋白治疗EAU的实验研究

目的 探讨重组小鼠IL-15/Fc融合蛋白治疗实验性自身免疫性葡萄膜炎(EAU)的效应和机制.方法 C57小鼠输注IRBPI-20抗原特异性T细胞,构建EAU模型,通过静脉注射重组IL-15/Fc融合蛋白,眼底镜和HE染色评价融合蛋白治疗EAU的疗效.用auto-MACS分离IRBPI-20抗原免疫小鼠T细胞,通过CFSE染色,3HTdR渗入抑制法,流式细胞仪,ELISA法检测IL-15/Fc融合蛋白对IRBPl-20特异性T细胞抗原特异性活化、增殖、分化和分泌炎症细胞因子的作用.结果 IL-15/Fc融合蛋白能有效抑制IRBPI-20特异性CD8 T细胞增殖、扩增、向CD44highCD62Llow效应细胞亚群的分化和分泌炎症性细胞因子.体内应用能有效抑制EAU的临床症状.结论 该重组IL-15/Fc融合蛋白能抑制IRBP1-20特异性CD8 T细胞活化、增殖、分化和分泌炎症性细胞因子,从而抑制EAU的炎症反应.

In vivo Effect of Recombined IL-15/Fc Fusion Protein on EAU

Obejctive To test the effect of recombined IL-15/Fc on experimental autoimmune uveitis(EAU) in mice.Methods EAU were induced in C57 mice by transferring activated T cells specific to the interphotoreceptor-binding protein(IRBP) 1-20 peptide.The mice were then treated with recombine IL-15/Fc fusion protein or IgG as controls.The severity of EAU were graded on a scale of 0 to 4 with half-point increment based on the type,number,and size of the lesions detected by funduscopic and HE staining.The IRBP1-20 sensitive CD8 T cells were isolated from the IRBP1-20 immune mice with auto-MACS.The in vitro effect of IL-15/Fc fusion protein on the proliferation,differentiation,expansion and production of inflammatory cytokines of the purified IRBP1-20 sensitive CD8 T cells were analyzed with 3HTdR,FACS and ELISA.Results IL-15/Fc fusion protein inhibited the activation,proliferation,expansion and production of inflammatory cytokines of the IRBP1-20 specific CD8 T cells,down regulated CD44highCD62Llow effect and CD8 CD62Llow activated T cell subsets,and consequently decreased the severity of EAU.Conclusion IL-15/Fc fusion proteins decrease the severity of EAU through inhibiting the proliferation,expansion,differentiation and production of inflammatory cytokines of CD8 T cells.