CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells
CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells
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DOI：
10.4049/jimmunol.173.5.3119
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发表时间：
2004-09-01
影响因子：
4.4
通讯作者：
Watanabe, M
中科院分区：
文献类型：
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作者：
Makita, S;Kanai, T;Watanabe, M
众所周知，肠道中的免疫反应保持在受控的炎症状态，这表明不仅调节性T细胞的主动抑制在正常的肠道稳态中起重要作用，而且其失调导致炎症性肠病的发展。在这项研究中，我们证明了CD 4（+）CD 25（亮）T细胞驻留在人类肠道固有层（LP）和功能保留的调节活动。所有人LP CD 4（+）T细胞（不考虑CD 25表达）均组成性表达CTLA-4、糖皮质激素诱导的TNFR家族相关蛋白和Foxp 3，且增殖较差。虽然LP CD 4（+）CD 25（-）T细胞显示活化和无反应性/记忆表型，但它们不保留调节活性。然而，在LP CD 4（+）CD 25（+）T细胞中，高水平表达CD 25的细胞（CD 4（+）CD 25（bright））抑制CD 4（+）CD 25（-）T细胞的增殖和各种细胞因子的产生。LP CD 4 + CD 25亮T细胞自身产生较少量的IL-2、IFN-γ和IL-10。有趣的是，在活动性炎症性肠病患者中，具有调节性T细胞活性的LP CD 4（+）CD 25（亮）T细胞显著增加。这些结果表明，正常和炎症肠粘膜中发现的CD 4（+）CD 25（亮）T细胞选择性抑制宿主免疫反应，因此可能有助于肠道免疫稳态。
It is well known that immune responses in the intestine remain in a state of controlled inflammation, suggesting that not only active suppression by regulatory T cells plays an important role in the normal intestinal homeostasis, but also its dysregulation leads to the development of inflammatory bowel disease. In this study, we demonstrate that the CD4(+)CD25(bright) T cells reside in the human intestinal lamina propria (LP) and functionally retain regulatory activities. All human LP CD4(+) T cells regardless of CD25 expression constitutively expressed CTLA-4, glucocorticoid-induced TNFR family-related protein, and Foxp3 and proliferate poorly. Although LP CD4(+)CD25(-) T cells showed an activated and anergic/memory phenotype, they did not retain regulatory activity. In LP CD4(+)CD25(+) T cells, however, cells expressing CD25 at high levels (CD4(+)CD25(bright)) suppressed the proliferation and various cytokine productions of CD4(+)CD25(-) T cells. LP CD4+CD25 bright T cells by themselves produced fewer amounts of IL-2, IFN-gamma, and IL-10. Interestingly, LP CD4(+)CD25(bright) T cells with regulatory T activity were significantly increased in patients with active inflammatory bowel disease. These results suggest that CD4(+)CD25(bright) T cells found in the normal and inflamed intestinal mucosa selectively inhibit the host immune response and therefore may contribute to the intestinal immune homeostasis.