Colitogenic Th1 cells are present in the antigen-experienced T cell pool in normal mice:: Control by CD4+ regulatory T cells and IL-10
Colitogenic Th1 cells are present in the antigen-experienced T cell pool in normal mice:: Control by CD4+ regulatory T cells and IL-10
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DOI：
10.4049/jimmunol.171.2.971
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发表时间：
2003-07-15
影响因子：
4.4
通讯作者：
Powrie, F
中科院分区：
文献类型：
--
作者：
Asseman, C;Read, S;Powrie, F
CD4（+）调节性T细胞已被证明可预防肠道炎症；然而，尚不清楚它们是通过阻止致结肠炎T细胞的启动，还是作为记忆T细胞库的一部分积极控制这些细胞来发挥作用。在这项研究中，我们描述了在CD4（+）CD45RB（低）群体中存在致结肠炎的Th1细胞。这些致病细胞在CD25（-）亚群中富集，且不是近期的胸腺迁出细胞。无菌小鼠的CD4（+）CD45RB（低）细胞将结肠炎转移给免疫缺陷受体的能力显著降低，这表明供体小鼠体内共生细菌的存在促使致结肠炎T细胞进入抗原经历/记忆T细胞库。这种具有潜在致病性的抗原经历T细胞群体在体内受到CD4（+）CD25（+）和CD4（+）CD25（-）细胞以白细胞介素 - 10（IL - 10）依赖的方式进行的T细胞介导的调节。此外，给未处理的成年小鼠施用抗白细胞介素 - 10受体单克隆抗体足以诱导结肠炎的发生。综上所述，这些数据表明致结肠炎的Th1细胞在正常小鼠中进入抗原经历库，但它们的功能受调节性T细胞和白细胞介素 - 10控制。有趣的是，白细胞介素 - 10对于CD4（+）CD25（+）T细胞介导的对由初始CD4（+）CD45RB（高）细胞转移所诱导的结肠炎的抑制并非绝对必需，这表明在对初始T细胞和抗原经历T细胞的调节中对白细胞介素 - 10的需求存在差异。
CD4(+) regulatory T cells have been shown to prevent intestinal inflammation; however, it is not known whether they act to prevent the priming of colitogenic T cells or actively control these cells as part of the memory T cell pool. In this study, we describe the presence of colitogenic Th1 cells within the CD4(+)CD45RB(low) population. These pathogenic cells enrich within the CD25(-) subset and are not recent thymic emigrants. CD4(+)CD45RB(low) cells from germfree mice were significantly reduced in their ability to transfer colitis to immune deficient recipients, suggesting the presence of commensal bacteria in the donor mice drives colitogenic T cells into the Ag-experienced/memory T cell pool. This potentially pathogenic population of Ag-experienced T cells is subject to T cell-mediated regulation in vivo by both CD4(+)CD25(+) and CD4(+)CD25(-) cells in an IL-10-dependent manner. Furthermore, administration of an anti-IL-10R mAb to unmanipulated adult mice was sufficient to induce the development of colitis. Taken together, these data indicate that colitogenic Th1 cells enter into the Ag-experienced pool in normal mice, but that their function is controlled by regulatory T cells and IL-10. Interestingly, IL-10 was not absolutely required for CD4(+)CD25(+) T cell-mediated inhibition of colitis induced by transfer of naive CD4(+)CD45RB(high) cells, suggesting a differential requirement for IL-10 in the regulation of naive and Ag-experienced T cells.