Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, Room EE1.17, 2333 CC Leiden, The Netherlands.
Cardiovasc Res. 2021 Dec 17;117(14):2755-2766. doi: 10.1093/cvr/cvaa286.
CD8+ T cells can differentiate into subpopulations that are characterized by a specific cytokine profile, such as the Tc17 population that produces interleukin-17. The role of this CD8+ T-cell subset in atherosclerosis remains elusive. In this study, we therefore investigated the contribution of Tc17 cells to the development of atherosclerosis.
Flow cytometry analysis of atherosclerotic lesions from apolipoprotein E-deficient mice revealed a pronounced increase in RORγt+CD8+ T cells compared to the spleen, indicating a lesion-specific increase in Tc17 cells. To study whether and how the Tc17 subset affects atherosclerosis, we performed an adoptive transfer of Tc17 cells or undifferentiated Tc0 cells into CD8-/- low-density lipoprotein receptor-deficient mice fed a Western-type diet. Using flow cytometry, we showed that Tc17 cells retained a high level of interleukin-17A production in vivo. Moreover, Tc17 cells produced lower levels of interferon-γ than their Tc0 counterparts. Analysis of the aortic root revealed that the transfer of Tc17 cells did not increase atherosclerotic lesion size, in contrast to Tc0-treated mice.
These findings demonstrate a lesion-localized increase in Tc17 cells in an atherosclerotic mouse model. Tc17 cells appeared to be non-atherogenic, in contrast to their Tc0 counterpart.
CD8+T 细胞可分化为具有特定细胞因子谱的亚群，如产生白细胞介素-17 的 Tc17 群体。这种 CD8+T 细胞亚群在动脉粥样硬化中的作用仍不清楚。在这项研究中，我们因此研究了 Tc17 细胞在动脉粥样硬化发展中的作用。
对载脂蛋白 E 缺陷小鼠动脉粥样硬化病变的流式细胞术分析显示，与脾脏相比，RORγt+CD8+T 细胞明显增加，表明 Tc17 细胞在病变中特异性增加。为了研究 Tc17 亚群是否以及如何影响动脉粥样硬化，我们将 Tc17 细胞或未分化的 Tc0 细胞过继转移到接受西方饮食喂养的 CD8-/-低密度脂蛋白受体缺陷小鼠中。通过流式细胞术，我们表明 Tc17 细胞在体内保留了高水平的白细胞介素-17A 产生。此外，Tc17 细胞产生的干扰素-γ水平低于其 Tc0 对应物。主动脉根部分析表明，与 Tc0 处理的小鼠相比，Tc17 细胞的转移并未增加动脉粥样硬化病变的大小。
这些发现表明在动脉粥样硬化小鼠模型中，病变局部 Tc17 细胞增加。与 Tc0 相比，Tc17 细胞似乎没有致动脉粥样硬化作用。
