Cao Ming, Ruan Lei, Huang Yi, Wang Jinli, Yan Jinhua, Sang Yu, Li Shanshan, Wang Guan, Wu Xiaofen
Department of Gerontology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Aging Dis. 2020 Dec 1;11(6):1471-1480. doi: 10.14336/AD.2020.0203. eCollection 2020 Dec.
Acquired immune responses mediated by CD4 T cells contribute to the initiation and progression of acute coronary syndrome (ACS). ACS patients show acquired immune system abnormalities that resemble the characteristics of autoimmune dysfunction described in the elderly. This study aimed to investigate the role of premature CD4 T cells senescence in ACS and the underlying mechanism. We compared the immunological status of 25 ACS patients, 15 young healthy individuals (C1), and 20 elderly individuals with absence of ACS (C2). The percentages of CD4 T lymphocyte subsets (including naïve, regulatory, memory and effector T cells) in peripheral blood were analyzed. In ACS patients, a significant expansion of CD4CD28 effector T cells and a decline of CD4CD25CD62LTreg cells were observed. In addition, patients with ACS showed an accelerated loss of CD4CD45RACD62L naïve T cells and a compensatory increase in the number of CD4CD45RO memory T cells. ACS patients demonstrated no significant difference in frequency of T cell receptor excision circles (TRECs) compared to age-matched healthy volunteers. The expression of p16 was increased while CD62L was decreased in CD4CD28 T cells of ACS patients. Compared to healthy donors, ACS patients demonstrated the lowest telomerase activity in both CD4CD28and CD4CD28 T cells. The serum levels of C-reactive protein, Cytomegalovirus IgG, IgG and IgG were significantly higher in ACS patients. The results suggested that the percentage of CD4 T cell subpopulations correlated with chronic infection, which contributes to immunosenescence. In conclusion, chronic infection induced senescence of premature CD4T cells, which may be responsible for the development of ACS.
由CD4 T细胞介导的获得性免疫反应有助于急性冠状动脉综合征（ACS）的发生和发展。ACS患者表现出获得性免疫系统异常，类似于老年人中描述的自身免疫功能障碍的特征。本研究旨在探讨过早的CD4 T细胞衰老在ACS中的作用及其潜在机制。我们比较了25例ACS患者、15名年轻健康个体（C1）和20名无ACS的老年人（C2）的免疫状态。分析了外周血中CD4 T淋巴细胞亚群（包括初始、调节性、记忆和效应T细胞）的百分比。在ACS患者中，观察到CD4CD28效应T细胞显著扩增，CD4CD25CD62LTreg细胞减少。此外，ACS患者的CD4CD45RACD62L初始T细胞加速丢失，CD4CD45RO记忆T细胞数量代偿性增加。与年龄匹配的健康志愿者相比，ACS患者的T细胞受体切除环（TREC）频率无显著差异。ACS患者CD4CD28 T细胞中p16表达增加而CD62L表达降低。与健康供体相比，ACS患者的CD4CD28和CD4CD28 T细胞中端粒酶活性最低。ACS患者的血清C反应蛋白、巨细胞病毒IgG、IgG和IgG水平显著更高。结果表明，CD4 T细胞亚群的百分比与慢性感染相关，这导致免疫衰老。总之，慢性感染诱导过早的CD4T细胞衰老，这可能是ACS发生的原因。
