使用抗CD20治疗1型糖尿病的非肥胖型糖尿病小鼠后Gr1+细胞的作用
发布时间：2012-10-08 14:22:57浏览次数：3436次来源：吉林大学白求恩第二医院 上海市第六人民医院 摘自:2012 Jan 1;188(1):294-301. Epub 2011 Dec 2.
研究表明Gr1（+）CD11b（+）细胞具有免疫调节功能，这些细胞可能对自身免疫性疾病起到重要作用。在这项研究中，我们研究Gr1（+）CD11b（+）细胞预防NOD小鼠患1型糖尿病的调节作用。在这项研究中，我们发现B细胞短时间的耗竭可以诱导Gr1（+）CD11b（+）细胞的增生。Gr1（+）CD11b（+）细胞不仅能直接抑制致糖尿病的T细胞的功能，并且能够诱导转化生长因子-β（TGF-β）依赖型调节性T细胞的分化。此外，我们发现在IL-10-、NO-和细胞接触依赖性方式下，Gr1（+）CD11b（+）细胞能够抑制致糖尿病的CD4和CD8 T细胞的功能。有趣的是，单抗Gr1单克隆抗体（mAb）治疗也能诱导Gr1(+)CD11b(+)细胞短时间的增生从而延缓NOD鼠糖尿病的发生发展，而我们的数据表明，对于胰岛的自身免疫性，Gr1(+)CD11b(+)细胞有助于针对其自身免疫性的免疫耐受的建立。因此，操控Gr1(+)CD11b(+)细胞可以被认为是一种防治1型糖尿病的新型的免疫疗法。
The role of Gr1+ cells after anti-CD20 treatment in type 1 diabetes in nonobese diabetic mice.
Studies suggest that Gr1(+)CD11b(+) cells have immunoregulatory function, and these cells may play an important role in autoimmune diseases. In this study, we investigated the regulatory role of Gr1(+)CD11b(+) cells in protecting against type 1 diabetes in NOD mice. In this study, we showed that temporary B cell depletion induced the expansion of Gr1(+)CD11b(+) cells. Gr1(+)CD11b(+) cells not only directly suppress diabetogenic T cell function but also can induce regulatory T cell differentiation in a TGF-β-dependent manner. Furthermore, we found that Gr1(+)CD11b(+) cells could suppress diabetogenic CD4 and CD8 T cell function in an IL-10-, NO-, and cell contact-dependent manner. Interestingly, single anti-Gr1 mAb treatment can also induce a transient expansion of Gr1(+)CD11b(+) cells that delayed diabetes development in NOD mice. Our data suggest that Gr1(+)CD11b(+) cells contribute to the establishment of immune tolerance to pancreatic islet autoimmunity. Manipulation of Gr1(+)CD11b(+) cells could be considered as a novel immunotherapy for the prevention of type 1 diabetes.
