scholarly journals Adaptive Immune Responses in Human Atherosclerosis

2020 ◽  
Vol 21 (23) ◽  
pp. 9322
Author(s):  
Silvia Lee ◽  
Benjamin Bartlett ◽  
Girish Dwivedi
Keyword(s):  
T Cells ◽  
Low Density Lipoprotein ◽  
Clinical Manifestations ◽  
Density Lipoprotein ◽  
Chronic Inflammatory Disease ◽  
Th2 Cells ◽  
Low Density ◽  
Heat Shock Protein 60 ◽  
Atherosclerosis Progression ◽  
Human Atherosclerosis

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.

Cellular immunity, low-density lipoprotein and atherosclerosis: Break of tolerance in the artery wall

2011 ◽  
Vol 106 (11) ◽  
pp. 779-786 ◽  
Author(s):  
Daniel Ketelhuth ◽  
Göran Hansson
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cellular Immunity ◽  
Inflammatory Responses ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Chronic Inflammatory Disease ◽  
Research Field ◽  
T Cell Subsets ◽  
Low Density

SummaryAtherosclerosis is a chronic inflammatory disease. Atherosclerotic plaques contain abundant immune cells that can dictate and effect inflammatory responses. Among them, T cells are present during all stages of the disease suggesting that they are essential in the initiation as well as the progression of plaque. Experimental as well as clinical research has demonstrated different T cell subsets, i.e. CD4+ Th1, Th2, Th17, and Treg as well as CD8+ and NKT cells in the plaque. Moreover, candidate antigens inducing T cell responses have been identified. Knowledge about the pathological role of these cells in atherogenesis may lead to development of new therapies. This review provides an overview of the research field of cellular immunity in atherosclerosis. It emphasises the events and findings involving antigen specific T cells, in particular low-density lipoprotein-specific T cells.

scholarly journals Oxidized low-density lipoproteins induce tissue factor expression in T-lymphocytes via activation of lectin-like oxidized low-density lipoprotein receptor-1

2019 ◽  
Vol 116 (6) ◽  
pp. 1125-1135 ◽  
Author(s):  
Giovanni Cimmino ◽  
Plinio Cirillo ◽  
Stefano Conte ◽  
Grazia Pellegrino ◽  
Giusi Barra ◽  
...  
Keyword(s):  
T Cells ◽  
T Lymphocytes ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Ros Generation ◽  
Low Density ◽  
Dependent Manner ◽  
Cd8 Cells ◽  
Human Carotid

Abstract Aims T-lymphocytes plays an important role in the pathophysiology of acute coronary syndromes. T-cell activation in vitro by pro-inflammatory cytokines may lead to functional tissue factor (TF) expression, indicating a possible contribution of immunity to thrombosis. Oxidized low-density lipoproteins (oxLDLs) are found abundantly in atherosclerotic plaques. We aimed at evaluating the effects of oxLDLs on TF expression in T cells and the role of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). Methods and results CD3+ cells were isolated from healthy volunteers. Gene, protein, and surface expression of TF, as well as of LOX-1, were assessed at different time-points after oxLDL stimulation. To determine whether oxLDL-induced TF was LOX-1 dependent, T cells were pre-incubated with an LOX-1 inhibiting peptide (L-RBP) or with an anti-LOX-1 blocking antibody. To exclude that TF expression was mediated by reactive oxygen species (ROS) generation, oxLDL-stimulated T cells were pre-incubated with superoxide dismutase + catalase or with 4-Hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), an intracellular free radical scavenger. Finally, to determine if the observed findings in vitro may have a biological relevance, the presence of CD3+/TF+/LOX-1+ cells was evaluated by immunofluorescence in human carotid atherosclerotic lesions. oxLDLs induced functionally active TF expression in T cells in a dose- and time-dependent manner, independently on ROS generation. No effect was observed in native LDL-treated T cells. LOX-1 expression was also induced by oxLDLs in a time- and dose-dependent manner. Pre-incubation with L-RBP or anti-LOX-1 antibody almost completely inhibited oxLDL-mediated TF expression. Interestingly, human carotid plaques showed significant infiltration of CD3+ cells (mainly CD8+ cells), some of which were positive for both TF and LOX-1. Conclusion oxLDLs induce functional TF expression in T-lymphocytes in vitro via interaction of oxLDLs with LOX-1. Human carotid atherosclerotic plaques contain CD3+/CD8+cells that express both TF and LOX-1, indicating that also in patients these mechanisms may play an important role.

scholarly journals Inhibition of T cell response to native low-density lipoprotein reduces atherosclerosis

2010 ◽  
Vol 207 (5) ◽  
pp. 1081-1093 ◽  
Author(s):  
Andreas Hermansson ◽  
Daniel F.J. Ketelhuth ◽  
Daniela Strodthoff ◽  
Marion Wurm ◽  
Emil M. Hansson ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Mhc Class Ii ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
T Cell Responses ◽  
Class Ii ◽  
Low Density ◽  
Cell Responses ◽  
Ldl Particles

Immune responses to oxidized low-density lipoprotein (oxLDL) are proposed to be important in atherosclerosis. To identify the mechanisms of recognition that govern T cell responses to LDL particles, we generated T cell hybridomas from human ApoB100 transgenic (huB100tg) mice that were immunized with human oxLDL. Surprisingly, none of the hybridomas responded to oxidized LDL, only to native LDL and the purified LDL apolipoprotein ApoB100. However, sera from immunized mice contained IgG antibodies to oxLDL, suggesting that T cell responses to native ApoB100 help B cells making antibodies to oxLDL. ApoB100 responding CD4+ T cell hybridomas were MHC class II–restricted and expressed a single T cell receptor (TCR) variable (V) β chain, TRBV31, with different Vα chains. Immunization of huB100tgxLdlr−/− mice with a TRBV31-derived peptide induced anti-TRBV31 antibodies that blocked T cell recognition of ApoB100. This treatment significantly reduced atherosclerosis by 65%, with a concomitant reduction of macrophage infiltration and MHC class II expression in lesions. In conclusion, CD4+ T cells recognize epitopes on native ApoB100 protein, this response is associated with a limited set of clonotypic TCRs, and blocking TCR-dependent antigen recognition by these T cells protects against atherosclerosis.

Atherosclerosis and thrombosis

2018 ◽  
Author(s):  
Lina Badimon ◽  
Gemma Vilahur
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Continuous Exposure ◽  
Low Density ◽  
Lipoprotein Particles ◽  
Atherosclerosis Progression

Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to microparticles a modulatory effect in the overall atherothrombotic process and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.

Atherosclerosis and thrombosis

2015 ◽  
Author(s):  
Lina Badimon ◽  
Gemma Vilahur
Keyword(s):  
Smooth Muscle ◽  
Inflammatory Response ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Muscle Cells ◽  
Low Density ◽  
Atherosclerosis Progression

Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the extracellular matrix and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated monocytes differentiate into macrophages which acquire a specialized phenotypic polarization (protective or harmful), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoprotein via low-density lipoprotein receptor-related protein-1 receptors. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Both lipid-laden vascular smooth muscle cells and macrophages release the procoagulant tissue factor, contributing to thrombus propagation. Platelets also participate in progenitor cell recruitment and drive the inflammatory response mediating the atherosclerosis progression. Recent data attribute to microparticles a potential modulatory effect in the overall atherothrombotic process. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be modulated.

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