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首页> 外文期刊>British journal of ophthalmology >Modulating phenotype and cytokine production of leucocytic retinal infiltrate in experimental autoimmune uveoretinitis following intranasal tolerance induction with retinal antigens.
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Modulating phenotype and cytokine production of leucocytic retinal infiltrate in experimental autoimmune uveoretinitis following intranasal tolerance induction with retinal antigens.

机译：鼻抗原耐受性鼻内诱导后，调节实验性自身免疫性葡萄膜视网膜炎中白细胞性视网膜浸润的表型和细胞因子产生。

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BACKGROUND/AIM: Nasal administration of retinal antigens induces systemic tolerance which results in suppression of experimental autoimmune uveoretinitis (EAU) when subsequently exposed to antigen. The aim was to establish if tolerance induction alters retinal infiltrating leucocyte phenotype and cytokine profile in tolerised animals when there is significantly reduced tissue destruction despite immunisation with retinal antigen. METHODS: Female Lewis rats were tolerised by intranasal administration with retinal extract (RE) before immunisation with RE to induce EAU. Control animals were administered phosphate buffered saline (PBS) intranasally. Post immunisation, daily clinical responses were recorded and at the height of disease, retinas were removed and either infiltrating leucocytes isolated for flow cytometric phenotype assessment and intracellular cytokine production, or chorioretina processed for immunohistochemistry. Fellow eyes were assessed for cytokine mRNA by semiquantitative RT-PCR. RESULTS: Flow cytometric analysis showed that before clinical onset of EAU there is no evidence of macrophage infiltration and no significant difference in circulating T cell populations within the retina. By day 14 a reduced retinal infiltrate in tolerised animals was observed and in particular a reduction in numbers of "activated" (with respect to CD4 and MHC class II expression) macrophages. Immunohistochemistry confirmed these findings and additionally minimal rod outer segment destruction was observed histologically. Cytokine analysis revealed that both IL-10 mRNA and intracellular IL-10 production was increased in tolerised eyes 7 days post immunisation. Although by day 14 post immunisation, IL-10 production was equivalent in both groups, a reduced percentage of IFN-gamma + macrophages and IFN-gamma + CD4+ T cells with increased percentage of IL-4+ CD4+ T cells were observed in tolerised animals. CONCLUSIONS: Leucocytic infiltrate is not only reduced in number but its distinct phenotype compared with controls implies a reduced activation status of infiltrating monocyts to accompany increased IL-10 and reduced IFN-gamma production in tolerised animals. This modulation may in turn contribute towards protection against target organ destruction in EAU.
机译：背景/目的：经鼻给予视网膜抗原可引起全身耐受，当其随后暴露于抗原时可抑制实验性自身免疫性葡萄膜视网膜炎（EAU）。目的是确定尽管用视网膜抗原免疫后组织破坏明显减少，但耐受诱导是否能改变耐受动物的视网膜浸润白细胞表型和细胞因子谱。方法：对雌性Lewis大鼠鼻内给予视网膜提取物（RE）可耐受，然后用RE免疫诱导EAU。对照动物经鼻内施用磷酸盐缓冲盐水（PBS）。免疫后，记录每天的临床反应，并在疾病高峰时摘除视网膜，并分离浸润的白细胞以进行流式细胞表型评估和细胞内细胞因子的产生，或处理脉络膜视网膜以进行免疫组织化学。通过半定量RT-PCR评估同卵眼睛的细胞因子mRNA。结果：流式细胞仪分析表明，在EAU临床发作之前，没有证据表明巨噬细胞浸润，并且视网膜内循环T细胞群体没有显着差异。到第14天，观察到耐受动物的视网膜浸润减少，特别是“激活的”（相对于CD4和MHC II类表达）巨噬细胞数目减少。免疫组织化学证实了这些发现，并且在组织学上还观察到最小的杆外部节段破坏。细胞因子分析显示，免疫后7天，耐受的眼睛中IL-10 mRNA和细胞内IL-10产量均增加。尽管到免疫后第14天，两组的IL-10产量相等，但在耐受的动物中观察到IFN-γ+巨噬细胞和IFN-γ+ CD4 + T细胞的百分比降低，而IL-4 + CD4 + T细胞的百分比提高。结论：与对照相比，白细胞浸润不仅数量减少，而且其独特的表型也暗示了浸润的单核细胞的活化状态降低，从而伴随着耐受动物IL-10的增加和IFN-γ产生的减少。这种调节反过来可能有助于防止EAU中靶器官的破坏。

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