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An Essential Role for Interleukin 10 in the Function of Regulatory T Cells That Inhibit Intestinal Inflammation

机译:白细胞介素10在抑制肠道炎症的调节性T细胞功能中的重要作用

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摘要

A T helper cell type 1–mediated colitis develops in severe combined immunodeficient mice after transfer of CD45RBhigh CD4+ T cells and can be prevented by cotransfer of the CD45RBlow subset. The immune-suppressive activities of the CD45RBlow T cell population can be reversed in vivo by administration of an anti-transforming growth factor β antibody. Here we show that interleukin (IL)-10 is an essential mediator of the regulatory functions of the CD45RBlow population. This population isolated from IL-10–deficient (IL-10−/−) mice was unable to protect from colitis and when transferred alone to immune-deficient recipients induced colitis. Treatment with an anti–murine IL-10 receptor monoclonal antibody abrogated inhibition of colitis mediated by wild-type (WT) CD45RBlow CD4+ cells, suggesting that IL-10 was necessary for the effector function of the regulatory T cell population. Inhibition of colitis by WT regulatory T cells was not dependent on IL-10 production by progeny of the CD45RBhigh CD4+ cells, as CD45RBlow CD4+ cells from WT mice were able to inhibit colitis induced by IL-10−/− CD45RBhigh CD4+ cells. These findings provide the first clear evidence that IL-10 plays a nonredundant role in the functioning of regulatory T cells that control inflammatory responses towards intestinal antigens.
机译:在CD45RB high CD4 + T细胞转移后,重度合并免疫缺陷小鼠中AT辅助细胞1型介导的结肠炎发展,可通过CD45RB low的共转移来预防子集。通过施用抗转化生长因子β抗体,可以体内逆转CD45RB T细胞群的免疫抑制活性。在这里,我们显示白介素(IL)-10是CD45RB low 人群调节功能的重要介体。从缺乏IL-10的(IL-10 -/-)小鼠中分离出的这种种群无法预防结肠炎,当单独转移到免疫缺陷的接受者时会诱发结肠炎。抗鼠IL-10受体单克隆抗体的治疗消除了野生型(WT)CD45RB low CD4 + 细胞介导的结肠炎抑制作用,表明IL-10是调节性T细胞群体的效应子功能所必需。 WT调节性T细胞抑制结肠炎并不依赖CD45RB high CD4 + 细胞子代产生IL-10,因为CD45RB low WT小鼠的CD4 + 细胞能够抑制IL-10 -/- CD45RB high CD4 + 单元格。这些发现提供了第一个明确的证据,即IL-10在调节T细胞的功能中起着非冗余作用,该T细胞控制着对肠道抗原的炎症反应。

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