Cui Yan, Shao Hui, Sun Deming, Kaplan Henry J
Department of Ophthalmology and Visual Sciences, Kentucky Lions Eye Center, University of Louisville, Louisville, Kentucky 40202, USA.
Invest Ophthalmol Vis Sci. 2009 Dec;50(12):5811-7. doi: 10.1167/iovs.09-3389. Epub 2009 May 20.
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-gamma(+) and IL-17(+) pathogenic T cells.
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.
Intraocular injection of the uveitogenic peptide (IRBP1-20), but not the nonuveitogenic peptide (IRBP161-180), inhibited the generation of IFN-gamma(+) 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 gammadelta T cells after subsequent systemic immunization with IRBP1-20. Absence of the gammadelta T-cell population prohibited the development of ACAID.
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 gammadelta T-cell population was reduced and was associated with decreased activation of IL-17(+) uveitogenic T cells.
前房内注射抗原可抑制迟发型超敏反应的发生，这一现象被称为前房相关免疫偏离（ACAID）。作者研究了前房内注射光感受器间类视黄醇结合蛋白（IRBP）肽对IFN-γ(+)和IL-17(+)致病性T细胞发育的影响。
将致葡萄膜炎性（IRBP1-20）或非致葡萄膜炎性（IRBP161-180）肽注入B6小鼠的前房（AC）。7天后，用致病性剂量的IRBP1-20佐剂对小鼠进行致敏。13天后，比较从治疗和未治疗小鼠脾脏中分离的T细胞的致病活性，并通过细胞内染色评估Th1和Th17 T细胞的数量。通过抗体染色和功能测定评估调节性T细胞活性。作者还比较了眼部注射至不同部位（包括前房、玻璃体腔和视网膜下间隙）对实验性自身免疫性葡萄膜炎（EAU）的抑制效果。
眼内注射致葡萄膜炎性肽（IRBP1-20）而非非致葡萄膜炎性肽（IRBP161-180）可抑制IFN-γ(+)和IL-17(+)致葡萄膜炎性T细胞的产生以及实验性自身免疫性葡萄膜炎（EAU）的发展。IRBP1-20而非IRBP161-180在前房内给药后，在用IRBP1-20进行后续全身免疫后，显著降低了循环γδ T细胞的数量。γδ T细胞群体的缺失阻止了ACAID的发展。
向前房内注射致葡萄膜炎性肽可通过调节Th1和Th17 IRBP特异性T细胞来抑制EAU的发展。循环γδ T细胞群体减少，并与IL-17(+)致葡萄膜炎性T细胞的活化降低有关。
