Phenotypic and functional characteristics of CD4+ CD39+ FOXP3+ and CD4+ CD39+ FOXP3neg T-cell subsets in cancer patients.
Phenotypic and functional characteristics of CD4+ CD39+ FOXP3+ and CD4+ CD39+ FOXP3neg T-cell subsets in cancer patients.
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DOI：
10.1002/eji.201142347
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发表时间：
2012-07
影响因子：
5.4
通讯作者：
Whiteside, Theresa L.
中科院分区：
文献类型：
--
作者：
Schuler, Patrick J.;Schilling, Bastian;Harasymczuk, Malgorzata;Hoffmann, Thomas K.;Johnson, Jonas;Lang, Stephan;Whiteside, Theresa L.
关键词：
人CD 4 + CD 39+调节性T（Treg）细胞水解外源性ATP并参与免疫抑制性腺苷的产生。它们包含两个T细胞亚群，其在介导抑制中的作用尚不清楚。对57例恶性肿瘤患者外周血淋巴细胞和6例肿瘤浸润淋巴细胞（TIL）中两种CD 4 + CD 39+亚群的频率进行了评价。在各种条件下培养使用免疫珠和细胞分选分离的CD 4 + CD 39+和CD 4 + CD 39-T细胞。通过多参数流式细胞术监测它们向CD 39 + FOXP 3 + CD 25+或CD 39 + FOXnegCD 25 neg细胞的转化。在发光测定中测量外源性ATP的水解。两种CD 4 + CD 39+细胞亚群在CD 25、FOXP 3、CTLA-4、CD 121 a、PD-1、CD 4、GARP的表达和细胞因子谱方面不同，在癌症患者的血液和肿瘤组织中以相等的频率积累。这两个子集的频率在癌症中显著增加。CD 39表达水平与亚群水解ATP的能力相关。与IL-2 + TGF-β孵育的常规CD 4 + CD 39阴性T细胞扩增以产生CD 4 + CD 39 + FOXP 3 + Treg细胞，而通过TCR和IL-2刺激的CD 4 + CD 39 + FOXP 3 + CD 25阴性亚群细胞转化为表达FOXP 3 + CTLA 4 + CD 25 + TGF-β的Treg细胞。在CD 4 + CD 39 + Treg细胞中，CD 4 + CD 39 + FOXP 3 + CD 25-亚群作为能够在环境信号激活后转化为Treg细胞的细胞库。
Human CD4+CD39+ regulatory T (Treg) cells hydrolyze exogenous ATP and participate in immunosuppressive adenosine production. They contain two T-cell subsets whose role in mediating suppression is not understood. Frequencies of both CD4+CD39+ subsets were evaluated in peripheral blood lymphocytes of 57 cancer patients and in tumor infiltrating lymphocytes (TILs) of 6 patients. CD4+CD39+ and CD4+CD39neg T cells isolated using immunobeads and cell sorting were cultured under various conditions. Their conversion into CD39+FOXP3+CD25+ or CD39+FOXnegCD25neg cells was monitored by multiparameter flow cytometry. Hydrolysis of exogenous ATP was measured in luminescence assays. Two CD4+CD39+ cell subsets differing in expression of CD25, FOXP3, CTLA-4, CD121a, PD-1, LAP, GARP and the cytokine profile accumulated with equal frequencies in the blood and tumor tissues of cancer patients. The frequency of both subsets was significantly increased in cancer. CD39 expression levels correlated with the subsets' ability to hydrolyze ATP. Conventional CD4+CD39neg T cells incubated with IL-2 + TGF-β expanded to generate CD4+CD39+FOXP3+ Treg cells, while CD4+CD39+FOXP3negCD25neg subset cells stimulated via the TCR and IL-2 converted to FOXP3+CTLA4+CD25+ TGF-β-expressing Treg cells. Among CD4+CD39+ Treg cells, the CD4+CD39+FOXP3negCD25neg subset serves as a reservoir of cells able to convert to Treg cells upon activation by environmental signals.
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影响因子：
5.4
作者：
Ndhlovu, Lishomwa C.;Leal, Fabio E.;Eccles-James, Ijeoma G.;Jha, Aashish R.;Lanteri, Marion;Norris, Philip J.;Barbour, Jason D.;Wachter, Douglas J.;Andersson, Jan;Tasken, Kjetil;Torheim, Eirik A.;Aandahl, Einar M.;Kallas, Esper G.;Nixon, Douglas F.
通讯作者：
Nixon, Douglas F.
影响因子：
20.3
作者：
Borsellino, Giovanna;Kleinewietfeld, Markus;Falk, Kirsten
通讯作者：
Falk, Kirsten
影响因子：
4.4
作者：
Kryczek, Ilona;Wu, Ke;Zou, Weiping
通讯作者：
Zou, Weiping
影响因子：
9
作者：
Bindea, Gabriela;Mlecnik, Bernhard;Fridman, Wolf-Herman;Galon, Jerome
通讯作者：
Galon, Jerome
影响因子：
11.2
作者：
Bergmann, Christoph;Strauss, Laura;Whiteside, Theresa L.
通讯作者：
Whiteside, Theresa L.