4.7 Article

Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self

期刊

CIRCULATION RESEARCH
卷 130, 期 10, 页码 1510-1530

出版社

LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.121.320090

关键词

atherosclerosis; coronary artery disease; endothelial cells; humans; plaque; atherosclerotic; T-lymphocytes

资金

  1. American Heart Association [181PA34170022, 20TPA3550008]
  2. NIA [R03 AG060182]
  3. NIHLBI [R01 HL 134830-01]
  4. Howard Hughes Medical Institute

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The immune microenvironment of human coronary atherosclerotic plaque was investigated using single-cell technology and in vitro assays. The study found a high proportion of αβT cells, which were primarily antigen-experienced memory cells and expressed an activation marker, HLA-DRA.
Background: Coronary artery disease is an incurable, life-threatening disease that was once considered primarily a disorder of lipid deposition. Coronary artery disease is now also characterized by chronic inflammation, notable for the buildup of atherosclerotic plaques containing immune cells in various states of activation and differentiation. Understanding how these immune cells contribute to disease progression may lead to the development of novel therapeutic strategies. Methods: We used single-cell technology and in vitro assays to interrogate the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. Results: In addition to macrophages, we found a high proportion of alpha beta T cells in the coronary plaques. Most of these T cells lack high expression of CCR7 and L-selectin, indicating that they are primarily antigen-experienced memory cells. Notably, nearly one-third of these cells express the HLA-DRA surface marker, signifying activation through their TCRs (T-cell receptors). Consistent with this, TCR repertoire analysis confirmed the presence of activated alpha beta T cells (CD4

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