Human Coronary Plaque T Cells Are Clonal and Cross-React to Virus and Self.
Abstract | BACKGROUND: 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 αβ 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 αβ T cells (CD4<CD8), exhibiting clonal expansion of specific TCRs. Interestingly, we found that these plaque T cells had TCRs specific for influenza, coronavirus, and other viral epitopes, which share sequence homologies to proteins found on smooth muscle cells and endothelial cells, suggesting potential autoimmune-mediated T-cell activation in the absence of active infection. To better understand the potential function of these activated plaque T cells, we then interrogated their transcriptome at the single-cell level. Of the 3 T-cell phenotypic clusters with the highest expression of the activation marker HLA-DRA, 2 clusters expressed a proinflammatory and cytolytic signature characteristic of CD8 cells, while the other expressed AREG ( amphiregulin), which promotes smooth muscle cell proliferation and fibrosis, and, thus, contributes to plaque progression. CONCLUSIONS: Taken together, these findings demonstrate that plaque T cells are clonally expanded potentially by antigen engagement, are potentially reactive to self- epitopes, and may interact with smooth muscle cells and macrophages in the plaque microenvironment.
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Authors | Roshni Roy Chowdhury, Jessica D'Addabbo, Xianxi Huang, Stefan Veizades, Koki Sasagawa, David M Louis, Paul Cheng, Jan Sokol, Annie Jensen, Alexandria Tso, Vishnu Shankar, Ben Shogo Wendel, Isaac Bakerman, Grace Liang, Tiffany Koyano, Robyn Fong, Allison N Nau, Herra Ahmad, Jayakrishnan Gopakumar, Robert Wirka, Andrew S Lee, Jack Boyd, Y Joseph Woo, Thomas Quertermous, Gunsagar Singh Gulati, Siddhartha Jaiswal, Yueh-Hsiu Chien, Charles Kwok Fai Chan, Mark M Davis, Patricia K Nguyen |
Journal | Circulation research
(Circ Res)
Vol. 130
Issue 10
Pg. 1510-1530
(05 13 2022)
ISSN: 1524-4571 [Electronic] United States |
PMID | 35430876
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)
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Chemical References |
- Antigens
- Epitopes
- HLA-DR alpha-Chains
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Topics |
- Antigens
- Clone Cells
(immunology)
- Coronary Artery Disease
(immunology)
- Endothelial Cells
- Epitopes
- HLA-DR alpha-Chains
- Humans
- Lymphocyte Activation
- Plaque, Atherosclerotic
(immunology)
- T-Lymphocytes
(immunology)
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