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用胶原蛋白脉冲树突状细胞进行疫苗接种可预防自发性多软骨炎小鼠模型的发病并减轻疾病严重程度。

Vaccination with collagen-pulsed dendritic cells prevents the onset and reduces the disease severity in the mouse model of spontaneous polychondritis.

作者信息

Sidhu M, Griffiths M M, Bradley D S

机构信息

Department of Microbiology and Immunology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202-9037, USA.

出版信息

Clin Exp Immunol. 2009 Sep;157(3):350-8. doi: 10.1111/j.1365-2249.2009.03968.x.

DOI:10.1111/j.1365-2249.2009.03968.x
PMID:19664142
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2745028/
Abstract

Immature dendritic cells (iDCs) have a tolerogenic potential due to low expression of important co-stimulatory cell surface molecules required for antigen presentation and induction of an effective immune response. We report here that injection of iDCs pulsed with chick type II collagen (CII) delayed the onset significantly and suppressed the severity of spontaneous polychondritis (SP) in the human leucocyte antigen (HLA)-DQ6alphabeta8alphabeta transgenic mouse model. Bone marrow-derived iDCs were pulsed in vitro with CII and transferred into 6-week-old HLA-DQ6alphabeta8alphabeta transgenic mice. Mice receiving CII-pulsed iDCs did not display any clinical signs of disease until 5.5 months of age, indicating the ability of the DC vaccine to delay significantly the onset of SP. Control groups receiving unpulsed iDCs or phosphate-buffered saline (PBS) developed polyarthritis at 3.5 months, as we have reported previously. The severity and incidence of disease was reduced in mice injected with CII-pulsed iDCs. Proinflammatory cytokines were in low to undetectable levels in the serum and tissue in the CII-pulsed iDC mice, correlating with the protection. This is the first evidence of iDC therapy controlling SP and suggests that iDC vaccination may provide a tool to reducing clinical manifestations in human inflammatory autoimmune disease such as relapsing polychondritis and rheumatoid arthritis.

摘要

未成熟树突状细胞(iDCs)具有致耐受性潜能,这是因为其在抗原呈递及诱导有效免疫反应所需的重要共刺激细胞表面分子表达水平较低。我们在此报告,在人类白细胞抗原(HLA)-DQ6αβ8αβ转基因小鼠模型中,注射用鸡II型胶原(CII)脉冲处理的iDCs可显著延迟自发性多软骨炎(SP)的发病,并减轻其严重程度。体外将骨髓来源的iDCs用CII脉冲处理后,转移至6周龄的HLA-DQ6αβ8αβ转基因小鼠体内。接受CII脉冲处理的iDCs的小鼠直到5.5月龄时都未表现出任何疾病临床症状,这表明DC疫苗有能力显著延迟SP的发病。如我们之前所报道,接受未脉冲处理的iDCs或磷酸盐缓冲盐水(PBS)的对照组在3.5月龄时出现了多关节炎。注射CII脉冲处理的iDCs的小鼠中疾病的严重程度和发病率降低。在CII脉冲处理的iDC小鼠的血清和组织中,促炎细胞因子处于低水平或无法检测到的水平,这与保护作用相关。这是iDC疗法控制SP的首个证据,并表明iDC疫苗接种可能为减轻人类炎性自身免疫性疾病(如复发性多软骨炎和类风湿性关节炎)的临床表现提供一种手段。

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本文引用的文献

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CD4+CD25+ T regulatory cells induced by LPS-activated bone marrow dendritic cells suppress experimental autoimmune uveoretinitis in vivo.脂多糖激活的骨髓树突状细胞诱导的CD4+CD25+调节性T细胞在体内抑制实验性自身免疫性葡萄膜视网膜炎。
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