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首页> 美国卫生研究院文献>Immunology >Adherent dendritic cells expressing high levels of interleukin-10 and low levels of interleukin-12 induce antigen-specific tolerance to experimental autoimmune encephalomyelitis
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Adherent dendritic cells expressing high levels of interleukin-10 and low levels of interleukin-12 induce antigen-specific tolerance to experimental autoimmune encephalomyelitis

机译：表达高水平白细胞介素10和低水平白细胞介素12的贴壁树突状细胞诱导对实验性自身免疫性脑脊髓炎的抗原特异性耐受

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We have previously shown that tolerance can be induced against acute experimental autoimmune encephalomyelitis (EAE) in Lewis rats by bone marrow-derived dendritic cells (DC) that have been pulsed in vitro with encephalitogenic myelin basic protein peptide 68–86 (MBP 68–86), and injected subcutaneously into healthy rats prior to immunization with MBP 68–86 plus complete Freund's adjuvant. To elucidate better the properties of tolerogenic DC, we here compared plastic-adherent DC with floating, non-adherent DC, which were cultured for 7 days in the presence of granulocyte–macrophage colony-stimulating factor plus interleukin-4 (IL-4). Adherent DC expressed high levels of IL-10 mRNA and protein, and low levels of IL-12 mRNA and showed high expression of CD54 compared with floating DC. Proliferation, nitrite concentration and capacity for antigen presentation were lower in adherent DC than in floating DC. There were no differences between adherent and floating DC regarding expression of CD11c, OX62, major histocompatibility complex class II, CD80, or CD86. Most importantly, we observed that adherent DC induced tolerance to EAE in vivo when injected subcutaneously into Lewis rats prior to immunization, while floating DC did not. Adherent DC-mediated tolerance to EAE was associated with augmented proliferation, nitric oxide production and frequency of apoptotic cells as well as with up-regulation of transforming growth factor-β (TGF-β) -expressing cells in T-cell areas of lymph nodes. Tolerance induction by adherent DC seems to be related to a nitric oxide–apoptosis pathway and to up-regulation of TGF-β-expressing cells.
机译：我们以前的研究表明，骨髓衍生的树突状细胞（DC）已在体外用脑致病性髓鞘碱性蛋白肽68–86（MBP 68–86）脉冲刺激，可以诱导Lewis大鼠急性实验性自身免疫性脑脊髓炎（EAE）耐受），然后在用MBP 68-86加上完全弗氏佐剂免疫之前，将其皮下注射到健康大鼠中。为了更好地说明耐受性DC的特性，我们在这里将塑料粘附DC与漂浮的非粘附DC进行了比较，在存在粒细胞-巨噬细胞集落刺激因子和白介素4（IL-4）的情况下，将它们粘附培养了7天。 。与浮动DC相比，粘附DC表达高水平的IL-10 mRNA和蛋白质，而低水平IL-12 mRNA，并显示高表达CD54。粘附DC的增殖，亚硝酸盐浓度和抗原呈递能力低于浮动DC。对于CD11c，OX62，II类主要组织相容性复合物，CD80或CD86的表达，粘附DC和漂浮DC之间没有差异。最重要的是，我们观察到在免疫前皮下注射Lewis大鼠皮下，粘附的DC会在体内诱导出对EAE的耐受性，而悬浮DC则不会。直流电介导的对EAE的耐受性与增殖，一氧化氮产生和凋亡细胞频率增加以及淋巴结T细胞区域中表达转化生长因子β（TGF-β）的细胞上调有关。粘附DC诱导的耐受性似乎与一氧化氮凋亡途径和表达TGF-β的细胞上调有关。

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