ApoB-Specific CD4⁺ T Cells in Mouse and Human Atherosclerosis

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 (T_H) 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 T_H subset definitions.
• ApoB-specific CD4+ T cells can simultaneously express mixed transcriptional programs and transition between T_H 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.