An increase in CD4+CD25+FOXP3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme
An increase in CD4+CD25+FOXP3+ regulatory T cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme
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DOI：
10.1215/15228517-2006-006
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发表时间：
2006-07-01
期刊：
影响因子：
15.9
通讯作者：
Lesniak, Maciej S.
中科院分区：
文献类型：
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作者：
El Andaloussi, Abdejabar;Lesniak, Maciej S.
CD4+CD25+免疫调节性T(Tr)细胞亚群占人类CD4+细胞的5%-10%。这些细胞在控制肿瘤免疫反应中起着至关重要的作用。在这项研究中，我们评估了Tr细胞在人多形性胶质母细胞瘤肿瘤浸润性淋巴细胞中的分布，并检测了脑和自体血液中Tr细胞的差异。10例脑胶质瘤标本被WHO分级为IV级星形细胞瘤。对照样本取自接受癫痫灶切除的患者。用流式细胞仪分析Tr细胞的频率，用实时定量聚合酶链式反应检测叉头盒P3(FOXP3)的表达。然后，我们检测CD62L、CD45RO和细胞毒性T淋巴细胞相关蛋白4(CTLA-4)的表达，并在体外评估Tr细胞的功能。胶质瘤浸润性淋巴细胞中表达FOXP3的CD4+CD25+T细胞数量与对照组相比有显著差异(P<；0.01)。这种差异在自体患者血液和对照血液的研究中进一步观察到。FOXP3mRNA在Tr细胞中高表达，在CD4+CD25-T细胞中弱表达。此外，CD62L和CTLA-4在胶质瘤Tr细胞中的表达明显高于对照组。这些细胞也呈CD45RO阳性。功能分析证实了胶质瘤患者Tr细胞的抑制活性。多形性胶质母细胞瘤患者外周血中CD4+CD25+FOXP3+T细胞的表达明显高于对照组。这种显示抑制活性的Tr细胞频率的增加可能在调节针对胶质瘤的免疫反应中发挥作用。鉴于这些发现，Tr细胞可能是恶性脑肿瘤免疫治疗的潜在靶点。
The subpopulation of CD4+CD25+ immunoregulatory T (Tr) cells constitutes 5%-10% of CD4+ cells in humans. These cells play a crucial role in the control of tumor immune response. In this study, we evaluated the distribution of Tr cells in tumor-infiltrating lymphocytes of human glioblastoma multiforme and examined the difference between the brain and autologous blood with respect to Tr cells. Glioma samples from 10 patients were classified as WHO grade IV astrocytoma. Control samples were obtained from patients undergoing resection of a seizure focus. The samples were analyzed by flow cytometry to determine the frequency of Tr cells and by real-time PCR for forkhead box P3 (FOXP3) expression. We then examined the expression of CD62L, CD45RO, and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and assessed the functionality of Tr cells in vitro. There was a significant difference in the number of FOXP3-expressing CD4+CD25+ T cells within glioma-infiltrating lymphocytes as compared to controls (P < 0.01). This difference was further observed in studies of autologous patient blood and control blood. The expression level of FOXP3 mRNA was high in Tr cells and weak in CD4+CD25- T cells. Moreover, the expression of CD62L and CTLA-4 was elevated in glioma Tr cells as compared to that in the controls. These cells were also CD45RO positive. Functional assays confirmed the suppressive activity of Tr cells in patients with glioma. The expression of CD4+CD25+FOXP3+ T cells was significantly higher in patients with glioblastoma multiforme than in controls. This increase in the frequency of Tr cells that display suppressive activity might play a role in modulation of the immune response against glioma. In light of these findings, Tr cells may represent a potential target for immunotherapy of malignant brain tumors.