TGF-β1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice
TGF-β1 plays an important role in the mechanism of CD4+CD25+ regulatory T cell activity in both humans and mice
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DOI：
10.4049/jimmunol.172.2.834
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发表时间：
2004-01-15
影响因子：
4.4
通讯作者：
Strober, W
中科院分区：
文献类型：
--
作者：
Nakamura, K;Kitani, A;Strober, W
在先前的研究中，我们已经表明，小鼠CD4(+)CD25(+)调节性T细胞以细胞表面和/或分泌形式产生高水平的转化生长因子-β1（TGF -β1），并且通过抗 - TGF -β阻断这种TGF -β1会削弱这些细胞在体外抑制试验中抑制CD25(-) T细胞增殖和B细胞Ig产生的能力。为了进一步支持TGF -β1在CD4(+)CD25(+) T细胞抑制作用中的角色，我们在本研究中表明，另一种TGF -β1阻断分子，即TGF -β1的重组潜伏期相关肽（rLAP），也能逆转小鼠CD4(+)CD25(+) T细胞以及它们的人类对应细胞CD4(+)CD25(高) T细胞的抑制作用。此外，我们表明在体外暴露于CD4(+)CD25(+) T细胞的CD25(-) T细胞表现出Smad - 2的激活和CD103的诱导，后者是一种TGF -β诱导的表面整合素。在进一步的研究中，我们表明虽然来自TGF -β1缺陷小鼠的CD4(+)CD25(+) T细胞在体外能够抑制CD25(-) T细胞增殖，但这些细胞在体内SCID转移模型中不能保护受体小鼠免受结肠炎的侵害，并且，此外，来自正常小鼠的CD4(+)LAP(+)而非CD4(+)LAP(-) T细胞在该模型中保护受体小鼠免受结肠炎的侵害。总之，这些研究表明CD4(+)CD25(+) T细胞产生的TGF -β1参与了这些细胞的抑制活性，特别是在它们调节肠道炎症的能力方面。
In previous studies, we have shown that murine CD4(+)CD25(+) regulatory T cells produce high levels of TGF-beta1 in a cell surface and/or secreted form, and blockade of such TGF-beta1 by anti-TGF-beta curtails the ability of these cells to suppress CD25(-) T cell proliferation and B cell Ig production in in vitro suppressor assays. In further support for the role of TGF-beta1 in suppression by CD4(+)CD25(+) T cells, we show in this study that another TGF-beta1-blocking molecule, recombinant latency-associated peptide of TGF-beta1 (rLAP), also reverses suppression by mouse CD4(+)CD25(+) T cells as well as their human counterparts, CD4(+)CD25(high) T cells. In addition, we show that CD25(-) T cells exposed to CD4(+)CD25(+) T cells in vitro manifest activation of Smad-2 and induction of CD103, the latter a TGF-beta-inducible surface integrin. In further studies, we show that while CD4(+)CD25(+) T cells from TGF-beta1 -deficient mice can suppress CD25(-) T cell proliferation in vitro, these cells do not protect recipient mice from colitis in the SCID transfer model in vivo, and, in addition, CD4(+)LAP(+), but not CD4(+)LAP(-) T cells from normal mice protect recipient mice from colitis in this model. Together, these studies demonstrate that TGF-beta1 produced by CD4(+)CD25(+) T cells is involved in the suppressor activity of these cells, particularly in their ability to regulate intestinal inflammation.