Human tumor-induced and naturally occurring Treg cells differentially affect NK cells activated by either IL-2 or target cells
Human tumor-induced and naturally occurring Treg cells differentially affect NK cells activated by either IL-2 or target cells
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DOI：
10.1002/eji.201141532
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发表时间：
2011-12-01
影响因子：
5.4
通讯作者：
Brandau, Sven
中科院分区：
文献类型：
--
作者：
Bergmann, Christoph;Wild, Clarissa A.;Brandau, Sven
NK细胞在消灭肿瘤细胞中发挥着至关重要的作用。天然存在的 (n) Treg 细胞和诱导的 (i) Treg 细胞是两个不同的 Treg 亚群。虽然过去已经研究了 nTreg 细胞与 NK 细胞的相互作用，但肿瘤 iTreg 细胞在调节 NK 细胞功能中的作用仍不清楚。肿瘤 iTreg 细胞是在自体未成熟 DC、头颈癌细胞以及 IL-2、IL-10 和 IL-15 存在下从 CD4(+)CD25(-) T 细胞产生的。研究了 iTreg 细胞和 nTreg 细胞对 NK 细胞表达 NKG2D、NKp44、CD107a 和 IFN-γ 以及 NK 肿瘤细胞溶解活性的影响。 iTreg 细胞 - 类似于重组 TGF-β 和 nTreg 细胞 - 在没有靶细胞接触的情况下抑制 IL-2 诱导的 NK 细胞活化。令人惊讶的是，与 nTreg 细胞相反，iTreg 细胞增强了靶细胞接触引起的 NK 细胞活性。 iTreg 细胞激活的 NK 细胞的溶细胞活性是通过穿孔素和 FasL 介导的。我们得出的结论是，在靶细胞不存在的情况下，肿瘤 iTreg 细胞抑制 IL-2 介导的 NK 细胞活性，而 NK 细胞的杀肿瘤活性则被 iTreg 细胞增强。我们的数据表明，肿瘤微环境中的 iTreg 细胞对人类 NK 活性存在复杂的、以前未被认识到的差异调节。
NK cells play a crucial role in the eradication of tumor cells. Naturally occurring (n) Treg cells and induced (i) Treg cells are two distinct Treg subsets. While the interaction of nTreg cells with NK cells has been investigated in the past, the role of tumor iTreg cells in the modulation of NK-cell function remains unclear. Tumor iTreg cells were generated from CD4(+)CD25(-) T cells in the presence of autologous immature DCs, head and neck cancer cells and IL-2, IL-10, and IL-15. The effect of iTreg cells and nTreg cells on the expression of NKG2D, NKp44, CD107a, and IFN-gamma by NK cells, as well as NK tumor-cytolytic activity, were investigated. iTreg cells - similar to recombinant TGF-beta and nTreg cells - inhibited IL-2-induced activation of NK cells in the absence of target cell contact. Surprisingly, and in contrast to nTreg cells, iTreg cells enhanced NK-cell activity elicited by target cell contact. The cytolytic activity of NK cells activated by iTreg cells was mediated via perforin and FasL. We conclude that tumor iTreg cells inhibited IL-2-mediated NK-cell activity in the absence of target cells, whereas the tumoricidal activity of NK cells was enhanced by iTreg cells. Our data suggest a complex, previously not recognized, differential regulation of human NK activity by iTreg cells in the tumor microenvironment.