Distribution, characterization, and induction of CD8+ regulatory T cells and IL-17-producing CD8+ T cells in nasopharyngeal carcinoma.

Distribution, characterization, and induction of CD8+ regulatory T cells and IL-17-producing CD8+ T cells in nasopharyngeal carcinoma.
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鼻咽癌中 CD8 调节性 T 细胞和产生 IL-17 的 CD8 T 细胞的分布、表征和诱导。

DOI:
10.1186/1479-5876-9-189
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发表时间:
2011-11-04
影响因子:
7.4
通讯作者:
Zeng YX
Zeng YX
中科院分区:
医学2区
文献类型:
--
作者:
Li J;Huang ZF;Xiong G;Mo HY;Qiu F;Mai HQ;Chen QY;He J;Chen SP;Zheng LM;Qian CN;Zeng YX

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CD 8+效应细胞通常在癌症患者中具有抗肿瘤功能。然而,CD 8 + Foxp 3+调节性T细胞(Tcregs)和产生白介素(IL)-17的CD 8 + T细胞(Tc 17细胞)也来源于CD 8 + T细胞谱系。它们在抗肿瘤反应中的作用在很大程度上仍然未知。在本研究中,我们的目的是调查的分布,特性,并在NPC患者的CD 8 + Tcregs和Tc 17细胞的生成。收集21例初诊鼻咽癌患者的外周血和肿瘤活检组织,沿着21例健康献血员的外周血。采用细胞内染色、四聚体染色和流式细胞仪(fluorescence-activated cell sorting,FACS)分析方法,检测血液和肿瘤组织中Tcregs和Tc 17细胞的生物学特性。使用增殖测定研究Tcregs的抑制功能,所述增殖测定涉及分选的CD 8 + CD 25 + T细胞与初始CD 4 + T细胞的体外共培养。我们观察到鼻咽癌患者肿瘤浸润淋巴细胞(TIL)中Tcregs和Tc 17细胞的患病率增加,以及外周血单个核细胞(PBMC)中的不同分布。细胞因子谱显示Tcregs表达高水平的IL-10和低水平的转化生长因子β,而Tc 17细胞表达高水平的肿瘤坏死因子α。有趣的是,这两个亚群在TIL中表达高水平的干扰素γ,并且Tcregs通过细胞接触依赖性机制在体外抑制幼稚CD 4 + T细胞增殖。此外,我们还证实了EB病毒潜伏膜蛋白(LMP)1和LMP 2抗原特异性Tcregs在NPC中的存在。我们的数据提供了新的见解CD 8 + T细胞亚群的组成和功能在鼻咽癌,这可能有重要的影响,鼻咽癌的免疫治疗。
CD8+ effector cells often have an antitumor function in patients with cancer. However, CD8+Foxp3+ regulatory T cells (Tcregs) and interleukin (IL)-17-producing CD8+ T cells (Tc17 cells) also derive from the CD8+ T cell lineage. Their role in the antitumor response remains largely unknown. In the present study, we aimed to investigate the distribution, characterization, and generation of CD8+ Tcregs and Tc17 cells in NPC patients. Peripheral blood and tumor biopsy tissues from 21 newly diagnosed patients with nasopharyngeal carcinoma (NPC) were collected, along with peripheral blood from 21 healthy donors. The biological characteristics of Tcregs and Tc17 cells from blood and tumor tissues were examined by intracellular staining, tetramer staining and fluorescence-activated cell sorting (FACS) analysis. The suppressive function of Tcregs was investigated using a proliferation assay that involved co-culture of sorted CD8+CD25+ T cells with naïve CD4+ T cells in vitro. We observed an increased prevalence of Tcregs and Tc17 cells among tumor-infiltrating lymphocytes (TILs) and different distribution among peripheral blood mononuclear cells (PBMCs) in NPC patients. Cytokine profiles showed that the Tcregs expressed a high level of IL-10 and low level of transforming growth factor β, whereas Tc17 cells expressed a high level of tumor necrosis factor α. Interestingly, both subsets expressed a high level of interferon γ in TILs, and the Tcregs suppressed naïve CD4+ T cell proliferation by a cell contact-dependent mechanism in vitro. Moreover, we demonstrated the existence of Epstein-Barr virus latent membrane protein (LMP) 1 and LMP2 antigen-specific Tcregs in NPC. Our data provide new insights into the composition and function of CD8+ T-cell subsets in NPC, which may have an important influence on NPC immunotherapy.
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