广西师范大学学报(自然科学版) ›› 2022, Vol. 40 ›› Issue (2): 191-199.doi: 10.16088/j.issn.1001-6600.2021022202

• • 上一篇    下一篇

正常来源CD4+CD25+细胞在小鼠肺癌模型中的抗肿瘤作用

周俊1,2,3, 陈舒曼1,2,3, 邢兵1, 陈雅静1,2,3, 李银玲1,2,3, 何柳1,2,3, 周祖平1,2,3, 蒲仕明1,2,3*   

  1. 1.广西师范大学 生命科学学院, 广西 桂林 541006;
    2.广西高校干细胞与医药生物技术重点实验室(广西师范大学), 广西 桂林 541004;
    3.广西师范大学 生物医学研究中心, 广西 桂林 541004
  • 收稿日期:2021-02-22 修回日期:2021-04-26 发布日期:2022-05-31
  • 通讯作者: 蒲仕明(1987—),男,四川南充人,广西师范大学助理研究员,硕士。E-mail:pushiming77@163.com
  • 基金资助:
    国家自然科学基金(81972700, 61827819); 广西自然科学基金(2018GXNSFBA281115); 广西大学生创新创业训练项目(202010602052)

Antitumor Effect of Normal Mice Derived CD4+CD25+ Cells in Mice Lung Cancer Model

ZHOU Jun1,2,3, CHEN Shuman1,2,3, XING Bing1, CHEN Yajing1,2,3, LI Yinling1,2,3, HE Liu1,2,3, ZHOU Zuping1,2,3, PU Shiming1,2,3*   

  1. 1. College of Life Sciences, Guangxi Normal University, Guilin Guangxi 541006, China;
    2. Guangxi Universities Key Laboratory of Stem Cell and Biopharmaceutical Technology (Guangxi Normal University), Guilin Guangxi 541004, China;
    3. Biomedical Research Center of Guangxi Normal University, Guangxi Normal University, Guilin Guangxi 541004
  • Received:2021-02-22 Revised:2021-04-26 Published:2022-05-31

摘要: CD4+CD25+细胞是一群具有免疫抑制活性的T细胞,又称为调节性T细胞(regulatory T cells, Tregs)。肿瘤发生中Tregs会抑制T细胞的活化,促进肿瘤的发生、发展,而正常生理来源的Tregs回输后产生的免疫调节作用是未知的。为探讨正常生理状态下Tregs的免疫调节作用,利用小鼠肺癌模型和细胞移植术,比较正常和荷瘤小鼠CD4+CD25+细胞移植对肿瘤生长、受体小鼠T细胞产生以及肺部病变的影响。结果显示:与对照组相比,移植正常CD4+CD25+细胞的小鼠生存期延长、肿瘤生长缓慢,其外周血与脾脏中T细胞及其亚群含量增加,小鼠肺部无明显病变;而移植荷瘤CD4+CD25+细胞的小鼠生存期缩短、肿瘤生长较快,其外周血与脾脏中T细胞及其亚群含量显著下降,肺部出现更严重弥散灶性病变。这些结果表明,正常来源CD4+CD25+细胞在小鼠肺癌模型中具有抗肿瘤作用。

关键词: 肺癌, CD4+CD25+细胞, 细胞移植, 肿瘤进程, 免疫调节

Abstract: CD4+CD25+ cells are a group of T cells with immunosuppressive activity, which are also known as regulatory T cells (Tregs). Tregs suppress T-cell activation and promote tumorigenesis and progression in tumorigenesis, whereas the immunomodulatory effects produced by Tregs of normal physiological origin upon return transfusion are unknown. To investigate the immunomodulatory effect of Tregs under normal physiological conditions, the effects of tumor growth and T-cell production and lung lesions were compared in normal and tumor-burdened mice of CD4+CD25+ cell transplantation by mouse lung cancer model and cell transplantation. The results showed that mice transplanted with normal CD4+CD25+ cells had longer survival, slower tumor growth, increased T-cell and their subpopulations in the peripheral blood and spleen, and no significant lesions in the lungs compared with the control group, while mice transplanted with tumor-bearing CD4+CD25+ cells had shorter survival, faster tumor growth, significantly decreased T-cell and their subpopulations in the peripheral blood and spleen, and more severe diffuse focal lesions in the lungs. These results indicated that normal-derived CD4+CD25+ cells had antitumor effects in the mouse lung cancer model.

Key words: lung cancer, CD4+CD25+ cells, cell transplants, tumor progression, immune regulation

中图分类号: 

  • R734.2
[1] ROMASZKO A M, DOBOSZYN′SKA A. Multiple primary lung cancer: A literature review[J]. Advances in Clinical and Experimental Medicine, 2018, 27(5): 725-730. DOI: 10.17219/acem/68631.
[2] NASIM F, SABATH B F, EAPEN G A. Lung cancer[J]. The Medical Clinics of North America, 2019, 103(3): 463-473. DOI: 10.1016/j.mcna.2018.12.006.
[3] MAO Y S, YANG D, HE J, et al. Epidemiology of lung cancer[J]. Surgical Oncology Clinics of North America, 2016, 25(3): 439-445. DOI: 10.1016/j.soc.2016.02.001.
[4] RODRIGUEZ-CANALES J, PARRA-CUENTAS E, WISTUBA I I. Diagnosis and molecular classification of lung cancer[J]. Cancer Treatment and Research, 2016, 170: 25-46. DOI: 10.1007/978-3-319-40389-2_2.
[5] WU T, DAI Y. Tumor microenvironment and therapeuticresponse[J]. Cancer Letters, 2017, 387: 61-68. DOI: 10.1016/j.canlet.2016.01.043.
[6] ARNETH B. Tumor Microenvironment[J]. Medicina, 2019, 56(1): 15. DOI: 10.3390/medicina56010015.
[7] GALDIERO M R, BONAVITA E, BARAJON I, et al. Tumor associated macrophages and neutrophils in cancer[J]. Immunobiology, 2013, 218(11): 1402-1410. DOI: 10.1016/j.imbio.2013.06.003.
[8] KALINSKI P, TALMADGE J E. Tumor immuno-environment in cancer progression and therapy[J]. Advances in Experimental Medicine and Biology, 2017, 1036: 1-18. DOI: 10.1007/978-3-319-67577-0_1.
[9] CHEN X, DU Y, HUANG Z. CD4+CD25+ treg derived from hepatocellular carcinoma mice inhibits tumor immunity[J]. Immunology Letters, 2012, 148(1): 83-89. DOI: 10.1016/j.imlet.2012.09.002.
[10] SOJKA D K, HUGHSON A, FOWELL D J. CTLA-4 is required byCD4+CD25+ Treg to control CD4+ T-cell lymphopenia-induced proliferation[J]. European Journal of Immunology, 2009, 39(6): 1544-1551. DOI: 10.1002/eji.200838603.
[11] FUJIO K, YAMAMOTO K, OKAMURA T, et al. Overview of LAG-3-Expressing, IL-10-producing regulatory T cells[J]. Current Topics in Microbiology and Immunology, 2017, 410: 29-45. DOI: 10.1007/82_2017_59.
[12] COLLISON L W, WORKMAN C J, KUO T T, et al. The inhibitory cytokine IL-35 contributes to regulatory T-cell function[J]. Nature, 2007, 450(7169): 566-569. DOI: 10.1038/nature06306.
[13] LI X L, YANG A M, HUANG H, et al. Induction of type 2 T helper cell allergen tolerance by IL-10-differentiated regulatory dendritic cells[J]. American Journal of Respiratory Cell and Molecular Biology, 2010, 42(2): 190-199. DOI: 10.1165/rcmb.2009-0023OC.
[14] JARNICKI A G, LYSAGHT J, TODRYK S, et al. Suppression of antitumor immunity by IL-10 and TGF-beta-producing T cells infiltrating the growing tumor: influence of tumor environment on the induction of CD4+ and CD8+ regulatory T cells[J]. Journal of Immunology, 2006, 177(2): 896-904. DOI: 10.4049/jimmunol.177.2.896.
[15] VANDENBARK A A, OFFNER H. Critical evaluation of regulatory T cells in autoimmunity: are the most potent regulatory specificities being ignored?[J]. Immunology, 2008, 125(1): 1-13. DOI: 10.1111/j.1365-2567.2008.02900.x.
[16] 肖捷, 杨丽萍, 肖健, 等. CD4+CD25+调节性T细胞在AIHA患者外周血中的表达及临床意义[J]. 中国医药科学, 2020, 10(16): 199-202.
[17] 王宇, 周建松, 许敏. CD4+CD25+Foxp3+调节性T细胞与肺癌患者预后的关系[J]. 热带医学杂志, 2021, 21(1): 61-65.
[18] WING K, SURI-PAYER E, RUDIN A. CD4+CD25+-regulatory T cells from mouse to man[J]. Scandinavian Journal of Immunology, 2005, 62(1): 1-15. DOI: 10.1111/j.1365-3083.2005.01634.x.
[19] ZHANG J H, DENG J H, YAO X L, et al. CD4(+)CD25(+) tregs as dependent factor in the course of bleomycin-induced pulmonary fibrosis in mice[J]. Experimental Cell Research, 2020, 386(1): 111700. DOI: 10.1016/j.yexcr.2019.111700.
[20] SHIM J, LEE E S, PARK S, et al. CD4(+)CD25(+) regulatory T cells ameliorate Behcet's disease-like symptoms in a mouse model[J]. Cytotherapy, 2011, 13(7): 835-847. DOI: 10.3109/14653249.2011.571245.
[21] 周奕辰, 王金岩. CD4+CD25+Treg细胞在小鼠Lewis肺癌生长及转移中的作用[J]. 中国免疫学杂志, 2019, 35(14): 1712-1716.
[22] CHAI J G. Cancer vaccination reprograms regulatory T cells into helper CD4 T cells to promote antitumor CD8 T-cell responses[J]. Immunotherapy, 2011, 3(5): 601-604. DOI: 10.2217/imt.11.22.
[23] SHARMA M D, HOU D Y, BABAN B, et al. Reprogrammed Foxp3+ regulatory T cells provide essential help to support cross-presentation and CD8+ T cell priming in naive mice[J]. Immunity, 2010, 33(6): 942-954. DOI: 10.1016/j.immuni.2010.11.022.
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