Activated T-effector seeds: cultivating atherosclerotic plaque through alternative activation.

Authors:
Maria M Xu
Maria M Xu
Department of Immunology
Patrick A Murphy
Patrick A Murphy
Pacific Vascular Research Laboratory
Anthony T Vella
Anthony T Vella
University of Connecticut Health Center
United States

Am J Physiol Heart Circ Physiol 2019 Jun 29;316(6):H1354-H1365. Epub 2019 Mar 29.

Department of Immunology, School of Medicine, University of Connecticut Health School of Medicine , Farmington, Connecticut.

Atherosclerosis is a chronic inflammatory pathology that precipitates substantial morbidity and mortality. Although initiated by physiological patterns of low and disturbed flow that differentially prime endothelial cells at sites of vessel branch points and curvature, the chronic, smoldering inflammation of atherosclerosis is accelerated by comorbidities involving inappropriate activation of the adaptive immune system, such as autoimmunity. The innate contributions to atherosclerosis, especially in the transition of monocyte to lipid-laden macrophage, are well established, but the mechanisms underpinning the infiltration, persistence, and effector dynamics of CD8 T cells in particular are not well understood. Adaptive immunity is centered on a classical cascade of antigen recognition and activation, costimulation, and effector cytokine secretion upon recall of antigen. However, chronic inflammation can generate alternative cues that supplant this behavior pattern and promote the retention and activation of peripherally activated T cells. Furthermore, the atherogenic foci that activated immune cell infiltrate are unique lipid-laden environments that offer a diverse array of stimuli, including those of survival, antigen hyporesponsiveness, and inflammatory cytokine expression. This review will focus on how known cardiovascular comorbidities may be influencing CD8 T-cell activation and how, once infiltrated within atherogenic foci, these T cells face a multitude of cues that skew the classical cascade of T-cell behavior, highlighting alternative modes of activation that may help contextualize associations of autoimmunity, viral infection, and immunotherapy with cardiovascular morbidity.

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Source
http://dx.doi.org/10.1152/ajpheart.00148.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6620674PMC

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June 2019
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