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<p>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<sup>+</sup> T cells in patients with angiographically verified CAD. APOB-reactive CD4<sup>+</sup> 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<sub>reg</sub>) cells. They shared signatures with CD4<sup>+</sup> T cells in mouse and human plaques, including expression of the plaque-homing chemokine receptor <i>CXCR6</i>. With increasing disease severity, the T<sub>reg</sub> signature was progressively and significantly lost. Conversely, APOB-specific T<sub>reg</sub> 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<sup>+</sup> T cells, which is replaced by a pro-inflammatory program in patients with severe CAD.</p>

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Loss of effector Treg signature in APOB-reactive CD4+ T cells in patients with coronary artery disease

  • 期刊论文

  • 发表日期：

    2025年6月18日

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  • Payel Roy,
  • Anusha Bellapu,
  • Sujit Silas Armstrong Suthahar,
  • Mohammad Oliaeimotlagh,
  • Qingkang Lyu,
  • Smriti Parashar,
  • Jeffrey Makings,
  • Runpei Wu,
  • Sunil Kumar,
  • Megh Mehta,
  • Austin W. T. Chiang,
  • Alessandro Sette,
  • Coleen A. McNamara,
  • Klaus Ley

摘要

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 (eTreg) 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 Treg signature was progressively and significantly lost. Conversely, APOB-specific Treg 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.