Regulation of interphotoreceptor retinoid-binding protein (IRBP)-specific th1 and th17 cells in anterior chamber-associated immune deviation (ACAID)

Abstract

Purpose. Intracameral (anterior chamber) injection of antigen inhibits the development of delayed-type hypersensitivity, a phenomenon known as anterior chamber-associated immune deviation (ACAID). The authors investigated the effect of intracameral injection of interphotoreceptor retinoid-binding protein (IRPB) peptides on the development of IFN-y+ and IL-17+ pathogenic T cells. Methods. A uveitogenic (IRBP1-20) or nonuveitogenic (IRBP161-180) peptide was injected into the anterior chamber (AC) of B6 mice. Seven days later, the mice were primed with a pathogenic dose of IRBP1-20 in adjuvant. Thirteen days later, the pathogenic activity of the T cells isolated from the spleens of treated and untreated mice were compared, and the numbers of Th1 and Th17 T cells were assessed by intracellular staining. Regulatory T-cell activity was assessed by antibody staining and functional assays. The authors also compared the effect of inhibition on EAU of ocular injection to various sites, including the AC, the vitreous cavity, and the subretinal space. Results. Intraocular injection of the uveitogenic peptide (IRBP1-20), but not the nonuveitogenic peptide (IRBP161-180), inhibited the generation of IFN-y+ and IL-17+ uveitogenic T cells and the development of experimental autoimmune uveitis (EAU). AC administration of IRBP1-20, but not IRBP161-180, significantly decreased the number of circulating yS T cells after subsequent systemic immunization with IRBP1-20. Absence of the yS T-cell population prohibited the development of ACAID. Conclusions. Injection of a uveitogenic peptide into the AC inhibited the development of EAU by regulation of Th1 and Th17 IRBP-specific T cells. The circulating yS T-cell population was reduced and was associated with decreased activation of IL-17+ uveitogenic T cells. © Association for Research in Vision and Ophthalmology.