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Review
. 2020 Dec 7;21(23):9322.
doi: 10.3390/ijms21239322.

Adaptive Immune Responses in Human Atherosclerosis

Silvia Lee  1   2 , Benjamin Bartlett  1   3 , Girish Dwivedi  1   3   4
Affiliations
Review

Adaptive Immune Responses in Human Atherosclerosis

Silvia Lee et al. Int J Mol Sci. .

Abstract

Atherosclerosis is a chronic inflammatory disease that is initiated by the deposition and accumulation of low-density lipoproteins in the artery wall. In this review, we will discuss the role of T- and B-cells in human plaques at different stages of atherosclerosis and the utility of profiling circulating immune cells to monitor atherosclerosis progression. Evidence supports a proatherogenic role for intraplaque T helper type 1 (Th1) cells, CD4+CD28null T-cells, and natural killer T-cells, whereas Th2 cells and regulatory T-cells (Treg) have an atheroprotective role. Several studies indicate that intraplaque T-cells are activated upon recognition of endogenous antigens including heat shock protein 60 and oxidized low-density lipoprotein, but antigens derived from pathogens can also trigger T-cell proliferation and cytokine production. Future studies are needed to assess whether circulating cellular biomarkers can improve identification of vulnerable lesions so that effective intervention can be implemented before clinical manifestations are apparent.

Keywords: B-cells; T-cells; adaptive immune response; human atherosclerosis.

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Conflict of interest statement

Girish Dwivedi has received speaker bureau fees from Amgen and Astra Zeneca not related to this publication. For the remaining authors, there are no conflicts of interest.

Figures

Figure 1
Figure 1
T-cell differentiation. (A) Following antigen presentation by antigen-presenting cells such as dendritic cells, naïve T-cells can differentiate to central memory or effector T-cells. This process is associated with the presence (+) or absence (−) of cell surface receptor expression on T-cells including costimulatory molecules and chemokine receptors, and functions including proliferation and cytotoxicity. (B) Depending on the costimulatory signals and the cytokines produced by antigen-presenting cells in the surrounding microenvironment, CD4+ T-cells express specific transcription factors that favor the differentiation into the different T-cell subsets. These subsets can be characterized by their distinctive cytokine secretion profile and associated effector functions.
Figure 2
Figure 2
Adaptive immune cells are involved in all stages of human atherosclerosis. Endothelial cells activation upregulates cell adhesion molecules and secretion of chemokines and so directs T-cells to the site of inflammation. T helper (Th)1 cells produce interferon-γ (IFNγ), a proatherogenic cytokine able to activate macrophages, inhibit proliferation, and reduce collagen production by smooth muscle cells. Th2 cells produce interleukin (IL)-4 and may be atheroprotective as they can inhibit Th1 cells. CD4+CD28null T-cells may damage cells in the vascular wall via the release of perforin and granzyme B. CD8+ T-cells may be proatherogenic via the production of IFNγ or protective by reducing macrophage content in the plaque. Treg cells can suppress Th1 and Th17 responses and increase smooth muscle cell proliferation through the secretion of cytokines (e.g., transforming growth factor (TGF)-β). Natural killer (NK)T cells exhibit proangiogenic and proinflammatory activities suggesting an involvement in plaque destabilization. Th17 and γδ T-cells are present in lesions but their roles are not well characterized. T-cells can be activated by heat shock proteins (e.g., HSP60), oxidized lipoproteins (oxLDL), or antigens derived from pathogens (e.g., cytomegalovirus (CMV) and Chlamydia pneumoniae (C. pneumoniae)).
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