肿瘤发生对小鼠胸腺发育及T细胞生成的影响

Effects of Tumorigenesis on Thymus Development and T Cell Production in Mice

胸腺(thymus)是机体的中枢免疫器官,在机体免疫系统发挥重要的作用。为了探索肺癌发生对小鼠胸腺发育的影响,阐明肿瘤状态下小鼠免疫功能的变化,本研究利用小鼠Lewis肺癌(Lewis lung carcinoma,LLC)细胞构建小鼠肺癌模型,采用HE染色分析小鼠胸腺形态学变化,利用流式细胞术分析小鼠胸腺、外周血中T细胞亚群的丰度,以及外周血中髓源性抑制细胞(myeloid-derived suppressor cells,MDSCs)的含量,并在分选MDSCs之后检测其对T细胞增殖的影响。结果显示:肿瘤状态下,小鼠胸腺指数下降,胸腺发生明显的萎缩,胸腺皮/髓质比下降;胸腺中各T细胞亚群(包括CD4^+CD8^-细胞、CD4^+CD8^-细胞、CD4^-CD8^+细胞和CD4^+CD8^-细胞)的绝对细胞数量均下降显著,未成熟的CD4^+CD8^-细胞含量下降明显;虽然CD4^-CD8^+细胞和CD4^+CD8^-细胞的含量在胸腺中显著增加,但是在外周血中呈现了相反的趋势。此外,肿瘤状态下外周血中MDSCs的丰度显著增加,且肿瘤来源的MDSCs表现出较正常来源的MDSCs更强的免疫抑制作用。以上信息提示,肿瘤发生中小鼠胸腺萎缩、T细胞数量显著减少的原因可能是大量MDSCs积累,且具有更强免疫抑制作用的肿瘤来源的MDSCs抑制了T细胞的增殖与活化。

Thymus is a central immune organ of the body and plays an important role in the immune system.In order to explore the effect of lung cancer on the development of thymus and clarify the changes of immune function under tumor state,mouse Lewis lung carcinoma(LLC)line was used to induce a mouse lung cancer model.HE staining was used to analyze the morphology of the mouse thymus.Flow cytometry was used to analyze the abundance of T cell subsets in the thymus and peripheral blood,the content of myeloidderived suppressor cells(MDSCs)in peripheral blood,and detect their effects on T cell proliferation after MDSCs were flow-sorted.The results showed that,under the tumor state,the thymus index of mice decreased,the thymus significantly atrophied,and the ratio of thymic cortex to medulla decreased.The absolute cell number of each T cell subset(including CD4-CD8-cells,CD4+CD8+cells,CD4^-CD8^+cells,CD4^+CD8^-cells)in the thymus decreased significantly,and the amount of immature CD4+CD8+cells also decreased significantly.Although the amounts of both CD4^-CD8^+and CD4^+CD8^-cells increased in the thymus,they showed the opposite trend in peripheral blood.In addition,the abundance of MDSCs in peripheral blood increased significantly,and tumor-derived MDSCs showed stronger immunosuppressive effects than normalderived MDSCs.These results suggests that the thymus atrophy in mice during tumorigenesis and the significant decrease of T cells may be due to the accumulation of a large number of MDSCs and the inhibition of T cell proliferation and activation by tumor-derived MDSCs,which had stronger immunosuppressive effects.