Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer.

Characteristics of CD4+CD25+ regulatory T cells in the peripheral circulation of patients with head and neck cancer.
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DOI:
10.1038/sj.bjc.6602407
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发表时间:
2005-03-14
影响因子:
8.8
通讯作者:
--
中科院分区:
医学1区
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--
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头颈部鳞状细胞癌(SCCHN)患者的抗肿瘤免疫力低下。这些患者中CD 4 + CD 25+(Treg)细胞的存在可能部分导致抗肿瘤免疫应答下调。为了评估SCCHN患者外周循环中Treg的频率和特征,我们使用多色流式细胞术。评估了与Treg和非Treg CD 4+淋巴细胞群体结合的CCR 7、CD 62 L、β链和膜联蛋白V的表达。Treg为Foxp 3+和GITR+。Treg频率在活动性疾病患者和治愈性治疗后无疾病证据(NED)的患者中显著升高。患者的Treg和非Treg CD 4 + T细胞在CCR 7 −和CD 62 L −细胞亚群中显著富集。虽然患者的Treg中含有较高比例的双阴性(CCR 7 − CD 62 L −)细胞,但大多数Treg是CCR 7 − CD 62 L+。Annexin V+ CD 4 + T细胞比例在患者组高于正常对照组(P<0.00005),Treg对细胞凋亡的敏感性显著高于non-Treg。与NC相比,在从患者获得的所有CD 4 + T细胞亚群中,CD 4 + T细胞的表达均降低。这些数据表明,SCCHN患者的Treg主要含有具有“效应”表型的T细胞,其结合膜联蛋白V并具有低表达,与其活化状态和外周循环中的快速周转一致。
Patients with squamous cell carcinoma of the head and neck (SCCHN) have depressed antitumour immunity. The presence of CD4+CD25+ (Treg) cells in these patients might be, in part, responsible for downregulation of antitumour immune responses. To evaluate the frequency and characteristics of Treg in the peripheral circulation of patients with SCCHN, we used multicolour flow cytometry. Expression of CCR7, CD62L, ζ chain and Annexin V binding to Treg and non-Treg CD4+ lymphocyte populations were evaluated. Treg were confirmed to be Foxp3+ and GITR+. The Treg frequency was significantly elevated in patients with active disease and those with no evidence of disease (NED) following curative therapies. Both Treg and non-Treg CD4+ T cells in patients were significantly enriched in CCR7− and CD62L− cell subsets. Although Treg in patients contained a higher proportion of double negative (CCR7−CD62L−) cells, the majority of Tregs were CCR7−CD62L+. The proportion of Annexin V+CD4+ T cells was higher in patients (P<0.00005) than normal controls (NC), and Treg were significantly more sensitive to apoptosis than non-Treg in patients and NC. Expression of ζ was reduced in all subsets of CD4+ T cells obtained from patients vs NC. The data suggest that Treg in patients with SCCHN largely contain T cells with the ‘effector’ phenotype, which bind Annexin V and have low ζ expression, consistent with their activation state and a rapid turnover in the peripheral circulation.
DOI: 10.1084/jem.193.11.1303
发表时间: 2001-06-04
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影响因子: --
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影响因子: 64.8
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