Jiang Hui-Rong, Muckersie Elizabeth, Robertson Marie, Forrester John V
Department of Ophthalmology, University of Aberdeen Medical School, Foresterhill, Aberdeen, Scotland, United Kingdom.
Invest Ophthalmol Vis Sci. 2003 Apr;44(4):1598-607. doi: 10.1167/iovs.02-0427.
To investigate the effect of maturation status of bone marrow-derived dendritic cells (BMDCs) on the in vivo immune response to interphotoreceptor retinoid-binding protein (IRBP) 161-180 peptide in experimental autoimmune uveoretinitis (EAU).
Immature and mature BMDCs were generated without or with the stimulation by lipopolysaccharide (LPS), and their mRNA cytokine profile and phenotype were analyzed by RNase protection assay and flow cytometry. The effect of immature and mature DCs in inducing antigen-specific T-cell proliferation and cytokine profile was further investigated in an IRBP peptide-induced model of EAU.
BMDCs generated in granulocyte-macrophage-colony-stimulating factor (GM-CSF) were relatively immature (i)DCs, as determined by flow cytometry and cytokine profile. However, stimulation with LPS induced these cells to become mature (m)DCs with higher levels of surface major histocompatibility complex (MHC)-II and costimulatory molecules and higher mRNA expression of IL-1alpha, -1beta, -6, and -12. Subcutaneous administration of iDCs induced a state of relative tolerance to the peptide induced-EAU, and the effect was lost after the DCs underwent maturation induced by in vitro exposure to LPS. In vitro, both iDCs and mDCs induced typical peptide-specific T-cell proliferation, but IFN-gamma production by uveitogenic T cells was markedly inhibited by iDCs. In vivo, peptide-loaded iDCs induced draining lymph node (DLN) cells to secrete a distinct pattern of cytokine: namely, increased IL-10 and IL-5 and decreased IFN-gamma and IL-2, indicating an altered immune responses to a low T-helper (Th) cell type 1 profile and a high Th2 profile after uveitogenic challenge.
The data suggest that induction of tolerance to an autoantigen by peptide-loaded DCs requires presentation of antigen by iDCs and involves the generation of a high-level IL-10 and IL-5 immune response in DLN cells.
研究骨髓来源的树突状细胞（BMDCs）的成熟状态对实验性自身免疫性葡萄膜视网膜炎（EAU）中光感受器间类视黄醇结合蛋白（IRBP）161 - 180肽体内免疫反应的影响。
在无脂多糖（LPS）刺激或有LPS刺激的情况下产生未成熟和成熟的BMDCs，通过核糖核酸酶保护试验和流式细胞术分析它们的mRNA细胞因子谱和表型。在IRBP肽诱导的EAU模型中进一步研究未成熟和成熟DCs在诱导抗原特异性T细胞增殖和细胞因子谱方面的作用。
通过流式细胞术和细胞因子谱测定，在粒细胞 - 巨噬细胞集落刺激因子（GM - CSF）中产生的BMDCs是相对未成熟的未成熟树突状细胞（iDCs）。然而，LPS刺激可诱导这些细胞成为成熟的成熟树突状细胞（mDCs），其表面主要组织相容性复合体（MHC） - II和共刺激分子水平更高，且IL - 1α、 - 1β、 - 6和 - 12的mRNA表达更高。皮下注射iDCs可诱导对肽诱导的EAU产生相对耐受状态，而在DCs经体外LPS诱导成熟后这种作用消失。在体外，iDCs和mDCs均可诱导典型的肽特异性T细胞增殖，但致葡萄膜炎T细胞产生的IFN - γ明显受到iDCs的抑制。在体内，负载肽的iDCs诱导引流淋巴结（DLN）细胞分泌不同模式的细胞因子：即IL - 10和IL - 5增加，IFN - γ和IL - 2减少，表明在致葡萄膜炎攻击后对低辅助性T（Th）1细胞类型和高Th2细胞类型的免疫反应发生了改变。
数据表明，负载肽的DCs诱导对自身抗原的耐受需要iDCs呈递抗原，并涉及在DLN细胞中产生高水平的IL - 10和IL - 5免疫反应。
