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Published on: May 6, 2014
ApoB-Specific CD4+ T Cells in Mouse and Human Atherosclerosis
Timoteo Marchini1,2,3, Sophie Hansen1,2, Dennis Wolf1,2
1Department of Cardiology and Angiology I, University Heart Center Freiburg, Hugstetterstraße 55, 79106 Freiburg, Germany.
Insights
Atherosclerosis involves an autoimmune response where CD4+ T-helper cells target Apolipoprotein B in LDL-C, driving plaque instability. These T cells exhibit unusual plasticity, challenging traditional immunology concepts.
Area of Science:
- Immunology
- Cardiovascular Medicine
- Autoimmunity
Background:
- Atherosclerosis is a chronic inflammatory arterial disease characterized by plaque formation.
- Traditionally viewed as myeloid-driven, emerging evidence points to an autoimmune component involving low-density lipoprotein cholesterol (LDL-C).
- CD4+ T-helper (TH) cells recognizing self-peptides from Apolipoprotein B (ApoB) are implicated in plaque development and instability.
Purpose of the Study:
- To review adaptive immune mechanisms in atherosclerosis, focusing on CD4+ T cells.
- To introduce novel technologies for detecting antigen-specific CD4+ T cells.
- To discuss the role of ApoB-driven autoimmunity in atherosclerosis.
Main Methods:
- Review of current literature on adaptive immunity in atherosclerosis.
- Discussion of recent advancements in single-cell detection technologies for antigen-specific T cells.
- Analysis of the phenotypic plasticity and functional heterogeneity of ApoB-specific CD4+ T cells.
Main Results:
- ApoB-reactive CD4+ T cells have been detected in humans and mice with atherosclerosis.
- These autoreactive T cells exhibit significant phenotypic plasticity, deviating from classical TH subset definitions.
- ApoB-specific CD4+ T cells can simultaneously express mixed transcriptional programs and transition between TH states.
Conclusions:
- ApoB-driven autoimmunity mediated by plastic CD4+ T cells is a key factor in atherosclerosis.
- Novel single-cell technologies are crucial for understanding these complex immune responses.
- Targeting ApoB-specific T cell autoimmunity may offer new therapeutic strategies for atherosclerosis.
Abstract:
Atherosclerosis is a chronic inflammatory condition of the arterial wall that leads to the formation of vessel-occluding plaques within the subintimal space of middle-sized and larger arteries. While traditionally understood as a myeloid-driven lipid-storage disease, growing evidence suggests that the accumulation of low-density lipoprotein cholesterol (LDL-C) ignites an autoimmune response with CD4+ T-helper (TH) cells that recognize self-peptides from Apolipoprotein B (ApoB), the core protein of LDL-C. These autoreactive CD4+ T cells home to the atherosclerotic plaque, clonally expand, instruct other cells in the plaque, and induce clinical plaque instability. Recent developments in detecting antigen-specific cells at the single cell level have demonstrated that ApoB-reactive CD4+ T cells exist in humans and mice. Their phenotypes and functions deviate from classical immunological concepts of distinct and terminally differentiated TH immunity. Instead, ApoB-specific CD4+ T cells have a highly plastic phenotype, can acquire several, partially opposing and mixed transcriptional programs simultaneously, and transit from one TH subset into another over time. In this review, we highlight adaptive immune mechanisms in atherosclerosis with a focus on CD4+ T cells, introduce novel technologies to detect ApoB-specific CD4+ T cells at the single cell level, and discuss the potential impact of ApoB-driven autoimmunity in atherosclerosis.
