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白细胞介素-17 通过释放转化生长因子β促进高级别胶质瘤来源的 CD4(+)CD25(+)Foxp3(+)T 细胞的免疫抑制能力。

Interleukin-17 facilitates the immune suppressor capacity of high-grade glioma-derived CD4 (+) CD25 (+) Foxp3 (+) T cells via releasing transforming growth factor beta.

机构信息

Department of Neurosurgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.

出版信息

Scand J Immunol. 2014 Aug;80(2):144-50. doi: 10.1111/sji.12185.

Abstract

High-grade glioma is a malignant tumour; the pathogenesis is to be further investigated. Interleukin (IL)-17 is an inflammatory cytokine. Chronic inflammation is a pathological feature of cancer. This study aimed to characterize the glioma-derived IL-17(+) regulatory T cells (Treg). In this study, single cells were isolated from surgically removed high-grade glioma tissue and examined by flow cytometry. The immune suppressor effect of IL-17(+) Tregs on CD8(+) T cells was assessed in vitro. The results showed that abundant IL-17(+) Tregs were found in high-grade glioma tissue. The immune suppressor molecule, transforming growth factor (TGF)-beta, was detected in the IL-17(+) Tregs. The proliferation of CD8(+) T cells was suppressed by culturing with the IL-17(+) Tregs, which was partially abrogated by neutralizing antibodies of either TGF-beta or IL-17 and completely abrogated by neutralizing antibodies against both TGF-beta and IL-17. In conclusion, IL-17(+) Tregs exist in the high-grade glioma tissue; this subset of T cells can suppress CD8(+) T cell activities via releasing TGF-beta and IL-17.

摘要

高级别神经胶质瘤是一种恶性肿瘤,其发病机制尚待进一步研究。白细胞介素(IL)-17 是一种炎症细胞因子。慢性炎症是癌症的一种病理特征。本研究旨在描述胶质瘤来源的白细胞介素 17(IL-17)阳性调节性 T 细胞(Treg)。在这项研究中,从手术切除的高级别神经胶质瘤组织中分离出单细胞,并通过流式细胞术进行检查。体外评估了 IL-17(+)Treg 对 CD8(+)T 细胞的免疫抑制作用。结果表明,高级别神经胶质瘤组织中存在大量的 IL-17(+)Treg。在 IL-17(+)Treg 中检测到免疫抑制分子转化生长因子(TGF)-β。与 IL-17(+)Treg 共培养可抑制 CD8(+)T 细胞的增殖,中和 TGF-β或 IL-17 的抗体可部分阻断该作用,而中和 TGF-β和 IL-17 的抗体则可完全阻断该作用。总之,IL-17(+)Treg 存在于高级别神经胶质瘤组织中;该 T 细胞亚群可以通过释放 TGF-β和 IL-17 来抑制 CD8(+)T 细胞的活性。

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