An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation.
An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation.
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白介素10在抑制肠炎的调节T细胞功能中的重要作用。
DOI：
10.1084/jem.190.7.995
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发表时间：
1999-10-04
影响因子：
15.3
通讯作者：
Powrie, F
中科院分区：
文献类型：
--
作者：
Asseman, C;Mauze, S;Leach, M W;Coffman, R L;Powrie, F
严重联合免疫缺陷小鼠在转移CD 45 RBhigh CD 4 + T细胞后发生1型T辅助细胞介导的结肠炎，并可通过CD 45 RBlow亚群的共转移来预防。通过给予抗转化生长因子β抗体，可在体内逆转CD 45 RB低T细胞群的免疫抑制活性。在这里，我们表明，白细胞介素（IL）-10是一个重要的调解人的调节功能的CD 45 RBlow人口。从IL-10缺陷（IL-10−/−）小鼠中分离的这一群体不能保护免受结肠炎的影响，当单独转移到免疫缺陷受体时，诱导结肠炎。用抗鼠IL-10受体单克隆抗体治疗消除了由野生型（WT）CD 45 RB低CD 4+细胞介导的结肠炎抑制，表明IL-10是调节性T细胞群的效应子功能所必需的。WT调节性T细胞对结肠炎的抑制不依赖于CD 45 RB high CD 4+细胞后代产生的IL-10，因为来自WT小鼠的CD 45 RB low CD 4+细胞能够抑制IL-10−/− CD 45 RB high CD 4+细胞诱导的结肠炎。这些发现提供了第一个明确的证据，表明IL-10在调节性T细胞的功能中起着非冗余的作用，调节性T细胞控制对肠道抗原的炎症反应。
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.