Depletion of CD4+CD25+ regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma
Depletion of CD4+CD25+ regulatory T cells can promote local immunity to suppress tumor growth in benzo[a]pyrene-induced forestomach carcinoma
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DOI：
10.3748/wjg.14.5797
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发表时间：
2008-10-14
影响因子：
4.3
通讯作者：
Shan, Yan-Shen
中科院分区：
文献类型：
--
作者：
Chen, Yi-Ling;Fang, Jung-Hua;Shan, Yan-Shen
目的：探讨CD4(+)CD25(+)调节性T细胞(Tregs)在去除CD25(+)Tregs前后在不同淋巴组织中的分布及其对肿瘤生长的局部促进作用。用单抗PC61清除CD4(+)CD25(+)Tregs。将小鼠分为BaP组、BaP+Ig G组、BaP+PC61组和对照组。解剖小鼠前胃进行组织学观察，并进行肿瘤细胞凋亡隧道试验。从不同淋巴组织中分选出CD4(+)CD25(+)Tregs，用流式细胞仪半定量和实时定量聚合酶链式反应分析Foxp3、IL-10和趋化因子受体的表达。结果：在16周和32周时，单独灌胃BaP的小鼠前胃乳头状瘤和肿瘤增加。胃周区域淋巴结中CD4(+)CD25(+)Tregs的比例明显高于其他淋巴组织。区域淋巴结中的这些CD4(+)CD25(+)Tregs表达较高水平的Foxp3和IL-10，富含CD62L-亚群，以及CCR1和CCR5趋化因子受体。BaP+PC61组小鼠肿瘤结节数明显减少，肿瘤体积明显减小，肿瘤细胞大量浸润，肿瘤细胞发生凋亡。结论：在肿瘤生长过程中，引流区域淋巴结中可诱导和激活的CD4(+)CD25(+)Tregs对宿主的局部免疫功能有抑制作用。去除CD4(+)CD25(+)Tregs可促进宿主局部免疫，抑制肿瘤生长。(C)2008年WJG出版社。版权所有。
AIM: To elucidate the distribution of CD4(+)CD25(+) regulatory T cells (Tregs) in different lymphoid tissues and its local enhancement on tumor growth before and after depletion of CD4(+)CD25(+) Tregs.METHODS: Female ICR mice were gavaged with benzo[a]pyrene (BaP) to induce forestomach carcinoma. CD4(+)CD25(+) Tregs were intra peritoneally depleted with monoclonal antibody PC61. These mice were divided into BaP-only, BaP + IgG, BaP + PC61, and control groups. The forestomach of mice was dissected for histological analysis, and tunnel test was performed for apoptosis of tumor cells. CD4(+)CD25(+) Tregs were sorted from different lymphoid tissues and expression of Foxp3, IL-10, and chemokine receptors was analyzed by flow cytometry semi-quantitative and real-time polymerase chain reaction.RESULTS: The mice gavaged with only BaP showed increased forestomach papilloma and carcinoma at wk 16 and 32. The proportion of CD4(+)CD25(+) Tregs was significantly higher in peri-stomach regional lymph nodes than in other lymphoid tissues. These CD4(+)CD25(+) Tregs in regional lymph nodes expressed higher levels of Foxp3 and IL-10, enriched in the CD62L-subset, and CCR1 and CCR5 chemokine receptors. In mice gavaged with BaP + PC61, the number of tumor nodules and tumor volume decreased significantly with massive infiltrating cells and apoptosis of tumor cells. In the draining regional lymph nodes, the number of CD4(+)CD25(+) Tregs also decreased significantly.CONCLUSION: Inducible and activated CD4(+)CD25(+) Tregs in the draining regional lymph nodes suppress host local immunity during tumor growth. Depletion of CD4(+)CD25(+) Tregs can promote host local immunity to suppress tumor growth. (C) 2008 The WJG Press. All rights reserved.