CD4+-CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer
CD4+-CD25+ T regulatory cells suppress NK cell-mediated immunotherapy of cancer
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DOI：
10.4049/jimmunol.176.3.1582
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发表时间：
2006-02-01
影响因子：
4.4
通讯作者：
Hayakawa, Y
中科院分区：
文献类型：
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作者：
Smyth, MJ;Teng, MWL;Hayakawa, Y
抑制 T 细胞介导的免疫反应的 CD4(+)CD25(+) 调节性 T 细胞 (Treg) 也可能调节有效免疫反应的其他方面。特别是，在这项研究中，我们表明Treg在体外和体内直接抑制NKG2D介导的NK细胞细胞毒性，有效抑制INK细胞介导的肿瘤排斥。在体外，Treg 被证明主要通过 TGF-β 依赖性机制且独立于 IL-10 抑制 NKG2D 介导的细胞溶解。过继转移的 Treg 抑制 RAG-1 缺陷小鼠的 NK 细胞抗转移功能。在通过 NKG2D 和激活的 IL-12 细胞因子激活 NK 细胞之前，Treg 的消耗显着增强了 NK 细胞介导的对肿瘤生长和转移的抑制。我们的数据说明了 Treg 抑制 NK 细胞抗肿瘤活性的至少一种机制，并强调了将 Treg 抑制与随后的 NK 细胞激活相结合以促进强大的先天抗肿瘤免疫的有效性。
CD4(+)CD25(+) regulatory T cells (Treg) that suppress T cell-mediated immune responses may also regulate other arms of an effective immune response. In particular, in this study we show that Treg directly inhibit NKG2D-mediated NK cell cytotoxicity in vitro and in vivo, effectively suppressing INK cell-mediated tumor rejection. In vitro, Treg were shown to inhibit NKG2D-mediated cytolysis largely by a TGF-beta-dependent mechanism and independently of IL-10. Adoptively transferred Treg suppressed NK cell antimetastatic function in RAG-1-deficient mice. Depletion of Treg before NK cell activation via NKG2D and the activating IL-12 cytokine, dramatically enhanced NK cell-mediated suppression of tumor growth and metastases. Our data illustrate at least one mechanism by which Treg can suppress NK cell antitumor activity and highlight the effectiveness of combining Treg inhibition with subsequent NK cell activation to promote strong innate antitumor immunity.