小鼠衰老所致“正虚”过程中免疫功能衰退表征的特点  

Characteristic of immune function decline in the process of“Declined of Vital Qi”caused by aging in mice

作　　者：田建辉 姚望[3] 阙祖俊 于盼 姚嘉良 罗斌 TIAN Jianhui;YAO Wang;QUE Zujun;YU Pan;YAO Jialiang;LUO Bin(Cancer Clinical Medical Center,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Institute of Oncology,Shanghai Municipal Hospital of Traditional Chinese Medicine,Shanghai University of Traditional Chinese Medicine,Shanghai 200071,China;Department of Oncology,Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China)

机构地区：[1]上海市中医医院暨上海中医药大学附属市中医医院肿瘤临床医学中心,上海200071 [2]上海市中医医院暨上海中医药大学附属市中医医院肿瘤研究所,上海200071 [3]上海中医药大学附属龙华医院肿瘤科,上海200032

出　　处：《中国肿瘤生物治疗杂志》2023年第11期950-956,共7页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金(No.81774166);上海市卫生健康委领军人才基金(No.2022LJ014);上海市炎癌转化病证生物学前沿研究基地课题(No.2021科技03-12)。

摘　　要：目的:基于小鼠渐进衰老模型探讨衰老所致“正虚”的免疫功能衰退表征的特点。方法:使用不同月龄(2、6、15月龄)C57BL/6小鼠,通过流式细胞术检测并比较小鼠外周血和脾组织中T细胞、髓源性抑制细胞(MDSC)及其亚群的丰度变化。结果:外周血中T细胞亚群表型为CD3^(+)CD4^(+)CD44-CD62L^(+)的幼稚CD4^(+)T细胞(2 vs 6月龄,P=0.137;2 vs 15月龄,P=0.004;6 vs15月龄,P=0.105)和表型为CD3^(+)CD8^(+)CD44-CD62L^(+)的幼稚CD8^(+)T细胞(2 vs 6月龄,P=0.179;2 vs 15月龄,P=0.001;6 vs15月龄,P=0.015)出现与衰老有关的细胞比例降低,差异具有统计学意义。表型为CD3^(+)CD4^(+)CD44^(+)CD62L^(+)的中央记忆CD8^(+)T细胞出现与衰老有关的比例升高,差异具有统计学意义(2 vs 6月龄,P=0.01;2 vs 15月龄,P=0.007;6 vs 15月龄,P=0.164)。对脾组织的检测结果具有与外周血相同特点。同时,CD8^(+)T细胞比例随衰老逐渐升高(2 vs 6月龄,P=0.027;2 vs 15月龄,P<0.001;6 vs15月龄,P<0.001);表型为CD8^(+)CD28^(+)的活化CD8^(+)T细胞亚群比例也出现随月龄增长的上升(2 vs 6月龄,P=0.863;2 vs 15月龄,P=0.016;6 vs 15月龄,P=0.024),差异均具有统计学意义。结论:衰老所致“正虚”过程中,不同免疫细胞亚群变化并不都反映免疫抑制特点,虽然总体免疫功能下降,但单一表型难以反应整体免疫功能变化。Objective:To investigate the characteristics of“Declined of Vital Qi”in the characterization of immune function decline caused by aging based on a mouse model of progressive aging.Methods:C57BL/6 mice of different months(2,6 and 15 months)were used to detect and compare the specific abundance of T cells,myeloid-derived suppressor cells(MDSC)and their subpopulations in peripheral blood and spleen of mice by flow cytometry.Results:In the peripheral blood,T cell subsets CD3+CD4+CD44-CD62L+naive CD4+T cells(2 vs 6 months old,P=0.137;2 vs 15 months old,P=0.004;6 vs 15 months old,P=0.105)and CD3+CD8+CD44-CD62L+naive CD8+T cells(2 vs 6 months old,P=0.179;2 vs 15 months old,P=0.001;6 vs 15 months old,P=0.015)showed a decrease in proportion to aging.However,the proportion of CD3+CD4+CD44+CD62L+central memory CD8+T cells increased with aging(2 vs 6 months old,P=0.01;2 vs 15 months old,P=0.007;6 vs 15 months old,P=0.164).The results in spleen experiment showed the same trend.At the same time,the proportion of CD8+T cells increased gradually with aging(2 vs 6 months old,P=0.027;2 vs 15 months old,P<0.001;6 vs 15 months old.P<0.001).The subsets of activated CD8+T cells with phenotype CD8+CD28+also increased with age(2 vs 6 months old,P=0.863;2 vs 15 months old,P=0.016;6 vs 15 months old,P=0.024).Conclusion:In the process of“Declined of Vital Qi”caused by aging,the changes of different immune cell subsets do not all reflect the characteristics of immunosuppression,although the overall immune function decreases.A single phenotype is difficult to reflect the change of overall immune function.

关 键 词：衰老 免疫功能 正虚 肺癌 T细胞 髓源性抑制细胞 

分 类 号：R392.12[医药卫生—免疫学] R228[医药卫生—基础医学]