Prolongation of survival following depletion of CD4+CD25+ regulatory T cells in mice with experimental brain tumors
Prolongation of survival following depletion of CD4+CD25+ regulatory T cells in mice with experimental brain tumors
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DOI：
10.3171/jns.2006.105.3.430
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发表时间：
2006-09-01
影响因子：
4.1
通讯作者：
Lesniak, Maciej S.
中科院分区：
文献类型：
--
作者：
El Andaloussi, Abdeljabar;Lesniak, Maciej S.
Object.调节性CD 4（+）CD 25（+）T细胞已被证明在免疫应答的调节中发挥重要作用。尽管这些细胞的存在与免疫抑制有关，但缺乏调节性T（Treg）细胞已被证明会诱导自身免疫。本研究的目的是确定Treg细胞在中枢神经系统（CNS）肿瘤中的作用。作者将同基因的GL 261肿瘤细胞植入C57 BL/6小鼠的大脑或侧腹。随后在特定时间点取出所得肿瘤，并通过进行流式细胞术分析Treg细胞的存在来分析肿瘤浸润淋巴细胞的存在。在另一个实验中，用抗CD 25单克隆抗体（mAb）注射治疗患有GL 261肿瘤的小鼠，以确定Treg细胞的耗竭是否可能对患有脑肿瘤的小鼠的存活时间产生影响。发现从患有GL 261肿瘤的小鼠分离的肿瘤浸润淋巴细胞与对照淋巴细胞相比在Treg细胞存在下显著增加（p < 0.05）。此外，在鼠脑肿瘤中分离的Treg细胞表达FoxP 3、CTLA-4和CD 62 L。用抗-CD 25 mAb治疗的小鼠比荷瘤对照动物存活显著更长（p < 0.05）。对存活动物大脑的分析显示，CD 4（+）CD 25（+）T细胞减少。本研究的结果表明，CD 4（+）CD 25（+）Treg细胞在抑制CNS肿瘤的免疫应答中起重要作用。因此，这些Treg细胞可能代表恶性胶质瘤免疫治疗的潜在新靶点。
Object. Regulatory CD4(+)CD25(+) T cells have been shown to play an important role in the regulation of the immune response. Whereas the presence of these cells has been associated with immune suppression, the lack of regulatory T (Treg) cells has been shown to induce autoimmunity. The purpose of this study was to define the role of Treg cells in tumors,of the central nervous system (CNS).Methods. The authors implanted syngeneic GL261 tumor cells in the brains or flanks of C57BL/6 mice. The resulting tumors were later removed at specific time points, and the presence of tumor-infiltrating lymphocytes was analyzed by performing flow cytometry for the presence of Treg cells. In a separate experiment, mice with GL261 tumors were treated with injections of anti-CD25 monoclonal antibody (mAb) to determine whether depletion of Treg cells may have an impact on the length of survival in mice with brain tumors.Tumor-infiltrating lymphocytes isolated from mice with GL261 tumors were found to have a significant increase in the presence of Treg cells compared with control lymphocytes (p < 0.05). Moreover, Treg cells isolated in murine brain tumors expressed FoxP3, CTLA-4, and CD62L. Mice treated with anti-CD25 mAb lived significantly longer than tumor-bearing control animals (p < 0.05). An analysis of brains in surviving animals showed a depletion of CD4(+)CD25(+) T cells.Conclusions. The results of this study indicate that CD4(+)CD25(+) Treg cells play an important role in suppressing the immune response to CNS tumors. These Treg cells may therefore represent a potentially novel target for immunotherapy of malignant gliomas.