Lin Guizhen, Zhang Lei, Yan Zheng, Jiang Wei, Wu Beibei, Xiong Xiaofang
The Department of Cardiology at Wuhan Third Hospital (Tongren Hospital of Wuhan University), 241 Pengliuyang Road, Wuchang District, Hubei Province, 430060, China.
Iran J Immunol. 2024 Dec 31;21(4):353-364. doi: 10.22034/iji.2024.97881.2536. Epub 2024 Dec 30.
CD8+ T cells have been found to accumulate in atherosclerotic plaques. However, the specific role of CD8+ T cell subsets in the development of atherosclerosis is still not fully understood.
To investigate the presence and functions of type 1 CD8+ T (Tc1) cells and interleukin-17 (IL-17)-producing CD8+ T (Tc17) cells.
Apolipoprotein E-deficient mice were fed a high-fat diet to induce atherosclerosis. Flow cytometry was used to identify and isolate aortic CD8+ T cell subsets, which were then cultured in vitro to assess their pro-inflammatory activities. The cholesterol content of the CD8+ T cell subsets was quantified.
T-box expressed in T cells (T-bet)+ Tc1 cells and retinoic acid-related orphan receptor gamma t (RORγt)+ Tc17 cells were found in the atherosclerotic aorta. Aortic CD8+ T cells showed lower pro-inflammatory activity compared to splenic counterparts, with less interferon-gamma (IFN-γ) (P <0.01) and tumor necrosis factor-alpha (TNF-α) production (P <0.01). Surprisingly, aortic CD8+ T cells expressed little IL-17 and interleukin-21 (IL-21) despite the presence of Tc17 cells. Aortic Tc1 and Tc17 cells expressed high levels of 2B4 and programmed cell death protein 1 (PD-1). Furthermore, aortic Tc1 and Tc17 cells had higher cholesterol contents than splenic CD8+ T cells (P <0.05, respectively). Cholesterol treatment decreased IFN-γ expression in Tc1 cells (P <0.001) and reduced IL-17 expression in Tc17 cells (P <0.001). Additionally, cholesterol up-regulated 2B4 and PD-1 on Tc1 (P <0.001) and Tc17 cells (P <0.001).
Aortic CD8+ T cells, particularly aortic Tc17 cells, are functionally exhausted in atherosclerosis, possibly due to the influence of cholesterol.
已发现CD8 + T细胞在动脉粥样硬化斑块中积聚。然而，CD8 + T细胞亚群在动脉粥样硬化发展中的具体作用仍未完全了解。
研究1型CD8 + T（Tc1）细胞和产生白细胞介素17（IL-17）的CD8 + T（Tc17）细胞的存在及功能。
给载脂蛋白E缺陷小鼠喂食高脂饮食以诱导动脉粥样硬化。采用流式细胞术鉴定和分离主动脉CD8 + T细胞亚群，然后在体外培养以评估其促炎活性。对CD8 + T细胞亚群的胆固醇含量进行定量分析。
在动脉粥样硬化的主动脉中发现了T细胞中表达的T盒（T-bet）+ Tc1细胞和视黄酸相关孤儿受体γt（RORγt）+ Tc17细胞。与脾脏中的CD8 + T细胞相比，主动脉CD8 + T细胞的促炎活性较低，产生的干扰素-γ（IFN-γ）较少（P <0.01），肿瘤坏死因子-α（TNF-α）也较少（P <0.01）。令人惊讶的是，尽管存在Tc17细胞，但主动脉CD8 + T细胞几乎不表达IL-17和白细胞介素21（IL-21）。主动脉Tc1和Tc17细胞高水平表达2B4和程序性细胞死亡蛋白1（PD-1）。此外，主动脉Tc1和Tc17细胞的胆固醇含量高于脾脏CD8 + T细胞（分别为P <0.05）。胆固醇处理降低了Tc1细胞中IFN-γ的表达（P <0.001），并降低了Tc17细胞中IL-17的表达（P <0.001）。此外，胆固醇上调了Tc1（P <0.001）和Tc17细胞（P <0.001）上的2B4和PD-1。
主动脉CD8 + T细胞，特别是主动脉Tc17细胞，在动脉粥样硬化中功能耗竭，可能是由于胆固醇的影响。
