OBJECTIVE: 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 CD44(high)CD62L(low) effect and CD8+ CD62L(low) 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.
OBJECTIVE: 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 CD44(high)CD62L(low) effect and CD8+ CD62L(low) 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.
Authors: Vinay V Vyas; Dominic Esposito; Terry L Sumpter; Trevor L Broadt; James Hartley; George C Knapp; Wei Cheng; Man-Shiow Jiang; John M Roach; Xiaoyi Yang; Steven L Giardina; George Mitra; Jason L Yovandich; Stephen P Creekmore; Thomas A Waldmann; Jianwei Zhu Journal: Biotechnol Prog Date: 2011-12-09