Related Experiment Video
Updated: Jun 3, 2026
Flow Cytometry Analysis of Immune Cells Within Murine Aortas
Published on: July 1, 2011
Single-Cell RNA Sequencing Reveals an Immune Landscape of CD4+ T Cells in Coronary Culprit Plaques With Acute
Shintaro Takeda1, Takuo Emoto1, Tomoya Yamashita1,2
1Division of Cardiovascular Medicine, Department of Internal Medicine (S.T., T.E., T. Yamashita, Y.S., T.H., H.O., K.-i.H.), Kobe University Graduate School of Medicine, Japan.
Insights
This study reveals CD4+ T cell characteristics in acute coronary syndrome (ACS) using single-cell analysis. These T cells show clonal expansion and may serve as therapeutic targets for preventing ACS events.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Genomics
Background:
- Acute coronary syndrome (ACS) is linked to plaque rupture and thrombosis, leading to heart damage or fatal arrhythmias.
- Previous research identified a distinct myeloid cell population in ACS culprit plaques via single-cell RNA sequencing.
- This study focuses on characterizing T cells at a single-cell level within ACS plaques.
Purpose of the Study:
- To perform single-cell RNA sequencing and T-cell receptor (TCR) repertoire analysis of T cells in ACS plaques.
- To identify distinct T cell subsets and their functional states within culprit lesions.
- To explore T cells as potential therapeutic targets for preventing ACS.
Main Methods:
- Single-cell RNA sequencing of CD45+ immune cells from chronic coronary syndrome (CCS) and ACS patient plaques.
- Unbiased TCR repertoire analysis of RNA extracted from ACS plaques.
- Velocity analysis to infer T cell differentiation pathways.
Main Results:
- CD4+ T cells clustered into effector, naive, cytotoxic, central memory, and regulatory subsets.
- ACS plaques showed a higher proportion of central memory CD4+ T cells compared to CCS plaques.
- Velocity analysis indicated T cell differentiation from naive to central memory, and then to effector cells in ACS plaques, alongside antigen-induced TCR clonal expansion.
Conclusions:
- This study provides the first single-cell characterization of CD4+ T cells in ACS.
- The findings suggest that CD4+ T cells are key players in ACS pathogenesis.
- CD4+ T cells represent a promising therapeutic target for managing and preventing ACS.
Background:
Acute coronary syndrome (ACS) involves plaque-related thrombosis, causing primary ischemic cardiomyopathy or lethal arrhythmia. We previously demonstrated a unique immune landscape of myeloid cells in the culprit plaques causing ACS by using single-cell RNA sequencing. Here, we aimed to characterize T cells in a single-cell level, assess clonal expansion of T cells, and find a therapeutic target to prevent ACS.
Methods:
We obtained the culprit lesion plaques from 4 patients with chronic coronary syndrome (chronic coronary syndrome plaques) and the culprit lesion plaques from 3 patients with ACS (ACS plaques) who were candidates for percutaneous coronary intervention with directional coronary atherectomy. Live CD45+ immune cells were sorted from each pooled plaque samples and applied to the 10× platform for single-cell RNA sequencing analysis. We also extracted RNA from other 3 ACS plaque samples and conducted unbiased TCR (T-cell receptor) repertoire analysis.
Results:
CD4+ T cells were divided into 5 distinct clusters: effector, naive, cytotoxic, CCR7+ (C-C chemokine receptor type 7) central memory, and FOXP3 (forkhead box P3)+ regulatory CD4+ T cells. The proportion of central memory CD4+ T cells was higher in the ACS plaques. Correspondingly, dendritic cells also tended to express more HLAs (human leukocyte antigens) and costimulatory molecules in the ACS plaques. The velocity analysis suggested the differentiation flow from central memory CD4+ T cells into effector CD4+ T cells and that from naive CD4+ T cells into central memory CD4+ T cells in the ACS plaques, which were not observed in the chronic coronary syndrome plaques. The bulk repertoire analysis revealed clonal expansion of TCRs in each patient with ACS and suggested that several peptides in the ACS plaques work as antigens and induced clonal expansion of CD4+ T cells.
Conclusions:
For the first time, we revealed single cell-level characteristics of CD4+ T cells in patients with ACS. CD4+ T cells could be therapeutic targets of ACS.
Registration:
URL: https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000046521; Unique identifier: UMIN000040747.
More Related Videos
05:54Preparation of a Non-Cardiomyocyte Cell Suspension for Single-Cell RNA Sequencing from a Post-Myocardial Infarction Adult Mouse Heart
Published on: February 3, 2023
08:51Author Spotlight: Integrated Multi-Omics Analysis for Unveiling Multicellular Immune Signatures in Clinical Heart Attack Cohorts
Published on: September 20, 2024
