CD69+CD4+CD25- T Cells, a New Subset of Regulatory T Cells, Suppress T Cell Proliferation through Membrane-Bound TGF-β1
CD69+CD4+CD25- T Cells, a New Subset of Regulatory T Cells, Suppress T Cell Proliferation through Membrane-Bound TGF-β1
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DOI：
10.4049/jimmunol.182.1.111
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发表时间：
2009-01-01
影响因子：
4.4
通讯作者：
Cao, Xuetao
中科院分区：
文献类型：
--
作者：
Han, Yanmei;Guo, Qiuli;Cao, Xuetao
肿瘤诱导的免疫抑制的潜在机制需要充分了解。调节性T(Treg)细胞在肿瘤免疫逃逸中发挥重要作用。到目前为止，已经描述了许多Treg细胞亚群可以通过不同的机制抑制T细胞反应。CD69通常被认为是一种激活标志物，但最近的研究表明，CD69可能在免疫应答中发挥调节作用。在这项研究中，我们发现肿瘤诱导的CD69(+)CD4(+)CD25(-)T细胞是一种新的CD4(+)Treg细胞亚群。随着肿瘤的进展，CD69(+)CD4(+)CD25(-)T细胞急剧增加，在晚期荷瘤小鼠中高达40%的CD4(+)T细胞。CD69(+)、CD4(+)、CD25(-)T细胞高表达CD122，但不表达Foxp3，分泌IL-10、转化生长因子-β1、IL-2和干扰素-γ，与已报道的CD4(+)Treg细胞亚群不同。CD69(+)、CD4(+)、CD25(-)T细胞是低反应性T细胞，可通过细胞-细胞接触的方式抑制CD4(+)T细胞的增殖。有趣的是，固定的CD69(+)CD4(+)CD25(-)T细胞仍然具有抑制活性，中和抗转化生长因子-β1的抗体可以阻断它们的抑制活性。我们发现CD69(+)CD4(+)CD25(-)T细胞表达膜结合的转化生长因子-β1，它介导抑制T细胞的增殖。此外，CD69的结合通过ERK激活维持CD69(+)、CD4(+)、CD25(-)T细胞膜结合的转化生长因子-β1的高表达。结果表明，CD69(+)、CD4(+)、CD25(-)T细胞是一种新的调节性CD4+T细胞亚群，具有Foxp3阴性表达、不分泌IL-10、高表达CD122和膜结合型转化生长因子-β1的特点，有助于进一步了解肿瘤免疫逃逸机制。免疫学杂志，2009,182：111-120。
The underlying mechanisms of tumor-induced immune suppression need to be fully understood. Regulatory T (Treg) cells have been shown to play an important role in tumor immune escape. Until now, many subsets of Treg cells have been described that can suppress T cell response via different mechanisms. CD69 is generally regarded as one of the activating markers; however, recent studies show that CD69 may exert regulatory function in the immune response. In this study, we have identified tumor-induced CD69(+)CD4(+)CD25(-) T cells as a new subset of CD4(+) Treg cells. CD69(+)CD4(+)CD25(-) T cells increase dramatically along tumor progression, with up to 40% of CD4(+) T cells in the advanced tumor-bearing mice. Distinct from the previously described CD4(+) Treg cell subsets, CD69(+)CD4(+)CD25(-) T cells express high CD122, but they do not express Foxp3 and secrete IL-10, TGF-beta 1, IL-2, and IFN-gamma. CD69(+)CD4(+)CD25(-) T cells are hyporesponsive and can suppress CD4(+) T cell proliferation in a cell-cell contact manner. Interestingly, the fixed CD69(+)CD4(+)CD25(-) T cells still have suppressive activity, and neutralizing Abs against TGF-beta 1 can block their suppressive activity. We found that CD69(+)CD4(+)CD25(-) T cells express membrane-bound TGF-beta 1, which mediates suppression of T cell proliferation. Furthermore, engagement of CD69 maintains high expression of membrane-bound TGF-beta 1 on CD69(+)CD4(+)CD25(-) T cells via ERK activation. Our results demonstrate that CD69(+)CD4(+)CD25(-) T cells act as a new subset of regulatory CD4+ T cells, with distinct characteristics of negative expression of Foxp3, no secretion of IL-10, but high expression of CD122 and membrane-bound TGF-beta 1. Our data contribute to the better understanding of mechanisms for tumor immune escape. The Journal of Immunology, 2009, 182: 111-120.