Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope.

Prevention of type 1 diabetes in mice by tolerogenic vaccination with a strong agonist insulin mimetope.
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通过强烈的激动剂胰岛素模拟蛋白的耐受性疫苗接种,预防小鼠中1型糖尿病。

DOI:
10.1084/jem.20110574
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发表时间:
2011-07-04
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
von Boehmer H
von Boehmer H
中科院分区:
其他
文献类型:
--
作者:
Daniel C;Weigmann B;Bronson R;von Boehmer H

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用胰岛素激动剂模拟表位进行亚免疫原性疫苗接种可将初始T细胞转化为调节性T细胞,并预防NOD小鼠的1型糖尿病。 1型糖尿病(T1D)是由自身反应性T细胞破坏分泌胰岛素的胰腺β细胞所致。胰岛素是自身免疫攻击的关键靶点。致糖尿病性T细胞克隆所识别的胰岛素表位与非肥胖糖尿病(NOD)小鼠的II类I - Ag7分子结合不佳,这导致肽 - MHC复合物的激动活性较弱。在此,我们描述了一种强激动性胰岛素模拟表位,它可在体内有效地将初始T细胞转化为Foxp3 +调节性T细胞,从而完全预防NOD小鼠的T1D。相比之下,天然胰岛素表位无效。用强激动性胰岛素模拟表位进行亚免疫原性疫苗接种可能代表一种预防有患病风险的人类T1D的新策略。
Subimmunogenic vaccination with an agonist mimetope of insulin converts naive T cells into regulatory T cells and prevents type 1 diabetes in NOD mice. Type 1 diabetes (T1D) results from the destruction of insulin-secreting pancreatic β cells by autoreactive T cells. Insulin is an essential target of the autoimmune attack. Insulin epitopes recognized by diabetogenic T cell clones bind poorly to the class II I-Ag7 molecules of nonobese diabetic (NOD) mice, which results in weak agonistic activity of the peptide MHC complex. Here, we describe a strongly agonistic insulin mimetope that effectively converts naive T cells into Foxp3+ regulatory T cells in vivo, thereby completely preventing T1D in NOD mice. In contrast, natural insulin epitopes are ineffective. Subimmunogenic vaccination with strongly agonistic insulin mimetopes might represent a novel strategy to prevent T1D in humans at risk for the disease.
气溶胶胰岛素诱导调节性CD8伽马三角细胞,可预防鼠胰岛素依赖性糖尿病。
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