冠状动脉疾病患者中载脂蛋白B反应性CD4 T细胞效应T细胞特征的丧失。
Loss of effector T signature in APOB-reactive CD4 T cells in patients with coronary artery disease.
作者信息
Roy Payel, Bellapu Anusha, Suthahar Sujit Silas Armstrong, Oliaeimotlagh Mohammad, Lyu Qingkang, Parashar Smriti, Makings Jeffrey, Wu Runpei, Kumar Sunil, Mehta Megh, Chiang Austin W T, Sette Alessandro, McNamara Coleen A, Ley Klaus
机构信息
Department of Physiology, Immunology Center of Georgia, Augusta University, Augusta, GA, USA.
Laboratory of Inflammation Biology, Center for Autoimmune Disease, La Jolla Institute for Immunology, La Jolla, CA, USA.
出版信息
Nat Cardiovasc Res. 2025 Jun 18. doi: 10.1038/s44161-025-00671-9.
Atherosclerosis underlies most coronary artery disease (CAD). It involves a significant autoimmune component against apolipoprotein B (APOB). In this study, we used short activation-induced marker (AIM) assays to characterize APOB-reactive CD4 T cells in patients with angiographically verified CAD. APOB-reactive CD4 T cells expressing CD25 and 4-1BB markers were the most abundant. Their frequency correlated positively with CAD severity. Transcriptomic analysis revealed that these cells were clonally expanded and significantly enriched in genes expressed in tissue-homing effector regulatory T (eT) cells. They shared signatures with CD4 T cells in mouse and human plaques, including expression of the plaque-homing chemokine receptor CXCR6. With increasing disease severity, the T signature was progressively and significantly lost. Conversely, APOB-specific T cells from patients with severe CAD gained glycolytic and interferon response signatures. We conclude that mild CAD is associated with a regulatory program in APOB-reactive CD4 T cells, which is replaced by a pro-inflammatory program in patients with severe CAD.
动脉粥样硬化是大多数冠状动脉疾病（CAD）的基础。它涉及针对载脂蛋白B（APOB）的重要自身免疫成分。在本研究中，我们使用短激活诱导标记（AIM）分析来表征经血管造影证实患有CAD的患者中APOB反应性CD4 T细胞。表达CD25和4-1BB标记的APOB反应性CD4 T细胞最为丰富。它们的频率与CAD严重程度呈正相关。转录组分析显示，这些细胞发生克隆性扩增，并且在组织归巢效应调节性T（eT）细胞中表达的基因中显著富集。它们与小鼠和人类斑块中的CD4 T细胞具有共同特征，包括斑块归巢趋化因子受体CXCR6的表达。随着疾病严重程度的增加，T细胞特征逐渐且显著丧失。相反，重度CAD患者的APOB特异性T细胞获得了糖酵解和干扰素反应特征。我们得出结论，轻度CAD与APOB反应性CD4 T细胞中的调节程序相关，而在重度CAD患者中该程序被促炎程序所取代。
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