Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients.
Immunosuppressive Treg cells acquire the phenotype of effector-T cells in chronic lymphocytic leukemia patients.
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DOI：
10.1186/s12967-018-1545-0
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发表时间：
2018-06-20
影响因子：
7.4
通讯作者：
Martinelli G
中科院分区：
文献类型：
--
作者：
De Matteis S;Molinari C;Abbati G;Rossi T;Napolitano R;Ghetti M;Di Rorà AGL;Musuraca G;Lucchesi A;Rigolin GM;Cuneo A;Calistri D;Fattori PP;Bonafè M;Martinelli G
在慢性淋巴细胞白血病（CLL）中，疾病的发作和进展受到特定CD 4 + T细胞亚群（如调节性T细胞（T细胞））行为的影响。在这里，我们集中在CLL患者的表型和功能表征TCLB，以提高我们的理解，这些细胞结合联合收割机免疫抑制和效应器样性能的推定机制。从新诊断的CLL患者（n = 25）和健康志愿者（n = 25）分离外周血单核细胞。通过流式细胞术评估TcB及其亚群的表型和功能特征。通过IFN-γ、IL-4、IL-17 A和IL-10分泌测定评价TH 1、TH 2、TH 17和Tcl 3细胞因子的体外分析。采用RT 2 Profiler PCR Array对84个基因组进行转录谱分析。使用精确非参数Mann-Whitney U检验进行统计分析。在所有的CLL样本中，我们发现分泌IL-10的T细胞亚群和T细胞亚群的频率显著增加，TH 2 IL-4+和TH 17 IL-17 A+细胞显著增加，IFN-γ/IL-10和IL-4/IL-10双释放CD 4 + T细胞的百分比更高。此外，我们还观察到先天免疫基因的上调和适应性免疫基因的下调。我们的数据显示，TCLs在CLL患者中向效应子样表型转变。这种多方面的行为伴随着改变的细胞因子谱和免疫基因的转录程序，导致CLL患者外周血环境中的免疫应答功能障碍。本文的在线版本（10.1186/s12967-018-1545-0）包含补充材料，可供授权用户使用。
In chronic lymphocytic leukemia (CLL) disease onset and progression are influenced by the behavior of specific CD4+ T cell subsets, such as T regulatory cells (Tregs). Here, we focused on the phenotypic and functional characterization of Tregs in CLL patients to improve our understanding of the putative mechanism by which these cells combine immunosuppressive and effector-like properties. Peripheral blood mononuclear cells were isolated from newly diagnosed CLL patients (n = 25) and healthy volunteers (n = 25). The phenotypic and functional characterization of Tregs and their subsets was assessed by flow cytometry. In vitro analysis of TH1, TH2, TH17 and Tregs cytokines was evaluated by IFN-γ, IL-4, IL-17A and IL-10 secretion assays. The transcriptional profiling of 84 genes panel was evaluated by RT2 Profiler PCR Array. Statistical analysis was carried out using exact non parametric Mann–Whitney U test. In all CLL samples, we found a significant increase in the frequency of IL-10-secreting Tregs and Tregs subsets, a significant rise of TH2 IL-4+ and TH17 IL-17A+ cells, and a higher percentage of IFN-γ/IL-10 and IL-4/IL-10 double-releasing CD4+ T cells. In addition, we also observed the up-regulation of innate immunity genes and the down-regulation of adaptive immunity ones. Our data show that Tregs switch towards an effector-like phenotype in CLL patients. This multifaceted behavior is accompanied by an altered cytokine profiling and transcriptional program of immune genes, leading to a dysfunction in immune response in the peripheral blood environment of CLL patients. The online version of this article (10.1186/s12967-018-1545-0) contains supplementary material, which is available to authorized users.
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影响因子：
2.7
作者：
Podhorecka, M;Dmoszynska, A;Wasik, E
通讯作者：
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Prentice, AG
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