肺癌模型小鼠肿瘤和主要免疫器官组织中调节性T细胞和NK细胞的数量变化及其意义

doi:10.13481/j.1671-587x.20160405

吉林大学学报(医学版) ›› 2016, Vol. 42 ›› Issue (04): 659-664.doi: 10.13481/j.1671-587x.20160405

肺癌模型小鼠肿瘤和主要免疫器官组织中调节性T细胞和NK细胞的数量变化及其意义

郑全辉, 王娜, 宋天姣, 曹倩文, 田雨, 郝小惠, 张爱红

华北理工大学河北省慢性病临床基础研究重点实验室, 河北唐山 063000

收稿日期:2016-01-02 发布日期:2016-07-20
通讯作者: 郑全辉,副教授,硕士研究生导师(Tel:0315-3724598,E-mail:zhqhdlp@sohu.com) E-mail:zhqhdlp@sohu.com
作者简介:郑全辉(1973-),男,河北省唐山市人,副教授,理学博士,主要从事肿瘤免疫学方面的研究。
基金资助:
国家自然科学基金资助课题（81373111）；河北省科技厅自然科学基金资助课题（H2013209019）；华北理工大学大学生创新创业训练计划项目资助课题（X2015153）

Changes of number of regulatory T cells and NK cells in tumor tissue and main immune organs of murine models of lung cancer and their significances

ZHENG Quanhui, WANG Na, SONG Tianjiao, CAO Qianwen, TIAN Yu, HAO Xiaohui, ZHANG Aihong

Hebei Key Laboratory for Chronic Diseases, North China University of Science and Technology, Tangshan 063000, China

Received:2016-01-02 Published:2016-07-20

摘要/Abstract

摘要：

目的：探讨肺癌小鼠CD4⁺CD25⁺Foxp3⁺调节性T细胞（Treg）和自然杀伤细胞（NK）在外周免疫器官和肿瘤组织中数量的变化，阐明其对肿瘤发展的影响。方法：C57BL/6小鼠分为Lewis肺癌细胞系（LLC）注射组和正常对照组，LLC注射组小鼠采用LLC腋窝注射制备皮下肿瘤模型，正常对照组小鼠采用生理盐水等量注射。采用细胞表面和细胞内特异荧光抗体染色和流式细胞术检测肺癌小鼠脾脏、淋巴结和肿瘤组织中CD4⁺CD25⁺T细胞、Treg细胞及脾脏组织中NK细胞数量。结果：与正常对照组比较，LLC注射组小鼠脾脏和淋巴结中CD4⁺CD25⁺ T细胞占CD4⁺T细胞比例及Foxp3⁺在CD4⁺CD25⁺T细胞中的表达比例明显升高（P < 0.05），CD4⁺CD25⁺Foxp3⁺ Treg细胞数量也明显升高（P < 0.05或P < 0.01）。LLC接种组小鼠肿瘤组织中CD4⁺CD25⁺ T细胞占CD4⁺T细胞比例及Foxp3⁺在CD4⁺CD25⁺T细胞中的表达比例明显高于脾脏和淋巴结（P < 0.05）。与正常对照组比较，LLC注射组小鼠脾脏组织中NK细胞比例明显降低（P < 0.05）。结论：肺癌小鼠主要免疫脏器官组织中Treg细胞比例和数量升高，NK细胞比例降低，其可促进肿瘤发展，抑制机体对肿瘤细胞的免疫应答。

关键词: 肺肿瘤, 调节性T细胞, 自然杀伤细胞

Abstract:

Objective: To explore the changes of number of CD4⁺CD25⁺foxp3⁺ regulatory T cells (Treg) and natural killer cells (NK) inthe peripheral immune organs and tumor tissue of the murine models of lung cancer,and to clarify their effects on the development of lung cancer. Methods: The C57BL/6 mice were divided into Lewis lung carcinoma cells (LLC) injection group and normal control group. The mice in LLC injection group were injected with LLC subcutaneously in the armpit to establish the tumor models,while the mice in normal control group were injected with the same amount of saline. The number of CD4⁺CD25⁺T cells,CD4⁺CD25⁺ foxp3⁺Tregs in the spleen,lymph nodes and lung cancer tissues,and the number of NK cells in the spleen tissue were labeled by cell surface or intracellular antibody staining,and detected by flow cytometry. Results: The ratios of CD4⁺CD25⁺T cells to CD4⁺T cells,foxp3⁺ cells to CD4⁺CD25⁺ T cells,and the number of CD4⁺CD25⁺foxp3⁺ Treg in the spleen and lymph nodes of the mice in LLC injection group were increased significantly compared with normal control group(P<0.05 or P<0.01). Moreover,the ratios of CD4⁺CD25⁺ T cells to CD4⁺ T cells and foxp3⁺ cells to CD4⁺CD25⁺T cells in the tumor tissue were significantly higher than those in the spleen and lymph nodes of the mice in LLC injection group. However,the ratio of NK cells in the spleen tissue of the mice in lung cancer group was significantly decreased compared with normal control group(P<0.05). Conclusion: The increase of ratio and the number of Treg cells and the decrease of ratio of NK cells in the main immune organs of lung cancer mice may promote the development of tumor and inhibit the immune response to cancer cells in vivo.

Key words: lung neoplasms, regulatory T cells, nature killer cells

中图分类号:

R392.11

郑全辉, 王娜, 宋天姣, 曹倩文, 田雨, 郝小惠, 张爱红. 肺癌模型小鼠肿瘤和主要免疫器官组织中调节性T细胞和NK细胞的数量变化及其意义[J]. 吉林大学学报(医学版), 2016, 42(04): 659-664.

ZHENG Quanhui, WANG Na, SONG Tianjiao, CAO Qianwen, TIAN Yu, HAO Xiaohui, ZHANG Aihong. Changes of number of regulatory T cells and NK cells in tumor tissue and main immune organs of murine models of lung cancer and their significances[J]. Journal of Jilin University Medicine Edition, 2016, 42(04): 659-664.

参考文献

[1] Campbell DJ,Koch MA. Phenotypic and functional specialization of FOXP3⁺regulatory T cells[J].Nat Rev Immunol,2011,11(2):119-130.

[2] Cheng M,Chen Y,Xiao W,et al. NK cell-based immunotherapy for malignant diseases[J]. Cell Mol Immunol,2013,10(3):230-252.

[3] 郑全辉,刘英文,张雪梅. 肺癌小鼠MDSC和T细胞变化[J].中国免疫学杂志,2015,31(5):595-599.

[4] Patel S,Vetale S,Teli P,et al.IL-10 production in non-small cell lung carcinoma patients is regulated by ERK,P38 and COX-2[J]. J Cell Mol Med,2012,16(3):531-544.

[5] Shi W,Li X,Cha Z,et al.Dysregulation of circulating follicular helper T cells in nonsmall cell lung cancer[J]. DNA Cell Biol,2014,33(6):355-360.

[6] Reppert S,Boross I,Koslowski M,et al.A role for T-bet-mediated tumour immune surveillance in anti-IL-17A treatment of lung cancer[J].Nat Commun,2011,2:600.

[7] Duan MC,Han W,Jin PW,et al. Disturbed Th17/Treg balance in patients with non-small cell lung cancer[J]. Inflammation,2015,38(6):2156-2165.

[8] 邹静,刘斌,陈雪华,等.肺癌患者外周血T淋巴细胞亚群变化特点及其临床意义[J].中国免疫学杂志,2010,26(11):1016-1020.

[9] 张瑞萍,徐冰心,王社论,等. 晚期非小细胞肺癌调节性T细胞与预后的关系[J]. 现代肿瘤医学, 2013,21(3):521-524.

[10] 赵霞,韩福才,苏文,等. 晚期肺癌患者外周血Treg细胞与NK细胞及其活化受体检测临床意义的探讨[J].中华肿瘤防治杂志,2011,18(13):1009-1012.

[11] 侯玉森,苏文,王艳峰,等.肺癌患者调节性T细胞与NK细胞活化受体NKG2D的相关性及其临床意义[J]. 肿瘤研究与临床,2012,24(9):597-599.

[12] Zhang Q,Furukawa K,Chen HH,et al. Metastatic potential of mouse Lewis lung cancer cells is regulated via ganglioside GM1 by modulating the matrix metalloprotease-9 localization in lipid rafts[J]. J Biol Chem,2006,281(26):18145-18155.

[13] Wang P,An F,Zhuang X,et al. Chronopharmacology and mechanism of antitumor effect of erlotinib in Lewis tumor-bearing mice[J].PLoS One,2014,9(7):e101720.

[14] Lindau D,Gielen P, Kroesen M,et al. The immunosuppressive tumour network:myeloid-derived suppressor cells,regulatory T cells and natural killer T cells[J].Immunology,2013,138(2):105-115.

[15] Hall BM,Verma ND,Tran GT,et al. Distinct regulatory CD4⁺T cell subsets;differences between naïve and antigen specific T regulatory cells[J]. Curr Opin Immunol,2011,23(5):641-647.

[16] Wieland E,Shipkova M. Lymphocyte surface molecules as immune activation biomarkers[J].Clin Biochem,2016,49(4/5):347-354.

[17] Feng LL,Wang X. Targeting foxp3⁺ regulatory T cells-related immunosuppression for cancer immunotherapy[J].Chin Med J (Engl),2010,123(22):3334-3342.

[18] Makkouk A,Weiner GJ. Cancer immunotherapy and breaking immune tolerance:new approaches to an old challenge[J]. Cancer Res,2015,75(1):5-10.

肺癌模型小鼠肿瘤和主要免疫器官组织中调节性T细胞和NK细胞的数量变化及其意义

Changes of number of regulatory T cells and NK cells in tumor tissue and main immune organs of murine models of lung cancer and their significances

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