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      T cell subsets and functions in atherosclerosis

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      Nature Reviews Cardiology
      Springer Science and Business Media LLC

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          Abstract

          Atherosclerosis is a chronic inflammatory disease of the arterial wall and the primary underlying cause of cardiovascular diseases. Approaches including in vivo imaging, cell-lineage tracing and knockout studies in mice, as well as clinical interventional studies and advanced mRNA sequencing techniques have drawn attention to the role of T cells as critical drivers and modifiers of the pathogenesis of atherosclerosis. CD4 + T cells are commonly found in atherosclerotic plaques. A large body of evidence indicates that T helper 1 (T H 1) cells have pro-atherogenic roles and regulatory T (T reg ) cells anti-atherogenic roles. However, T reg cells can become pro-atherogenic. The roles in atherosclerosis of other T H cell subsets such as T H 2, T H 9, T H 17, T H 22, follicular helper T cells and CD28 – T cells, as well as other T cell subsets including CD8 + T cells and γδT cells, are less well understood. Moreover, some T cells seem to have both pro-atherogenic and anti-atherogenic functions. In this Review, we summarize the knowledge on T cell subsets, their functions in atherosclerosis and the process of T cell homing to atherosclerotic plaques. Much of our understanding of T cell roles in atherosclerosis is based on findings from experimental models. Translating these findings into human disease is challenging, but much needed. Targeting T cells and their specific cytokines are attractive pathways for developing new preventative and therapeutic approaches including potential T cell-related therapies for atherosclerosis.

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          Most cited references149

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          Decisions about dendritic cells: past, present, and future.

          A properly functioning adaptive immune system signifies the best features of life. It is diverse beyond compare, tolerant without fail, and capable of behaving appropriately with a myriad of infections and other challenges. Dendritic cells are required to explain how this remarkable system is energized and directed. I frame this article in terms of the major decisions that my colleagues and I have made in dendritic cell science and some of the guiding themes at the time the decisions were made. As a result of progress worldwide, there is now evidence of a central role for dendritic cells in initiating antigen-specific immunity and tolerance. The in vivo distribution and development of a previously unrecognized white cell lineage is better understood, as is the importance of dendritic cell maturation to link innate and adaptive immunity in response to many stimuli. Our current focus is on antigen uptake receptors on dendritic cells. These receptors enable experiments involving selective targeting of antigens in situ and new approaches to vaccine design in preclinical and clinical systems.
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            Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry.

            A novel instrument for real time analysis of individual biological cells or other microparticles is described. The instrument is based on inductively coupled plasma time-of-flight mass spectrometry and comprises a three-aperture plasma-vacuum interface, a dc quadrupole turning optics for decoupling ions from neutral components, an rf quadrupole ion guide discriminating against low-mass dominant plasma ions, a point-to-parallel focusing dc quadrupole doublet, an orthogonal acceleration reflectron analyzer, a discrete dynode fast ion detector, and an 8-bit 1 GHz digitizer. A high spectrum generation frequency of 76.8 kHz provides capability for collecting multiple spectra from each particle-induced transient ion cloud, typically of 200-300 micros duration. It is shown that the transients can be resolved and characterized individually at a peak frequency of 1100 particles per second. Design considerations and optimization data are presented. The figures of merit of the instrument are measured under standard inductively coupled plasma (ICP) operating conditions ( 900 for m/z = 159, the sensitivity with a standard sample introduction system of >1.4 x 10(8) ion counts per second per mg L(-1) of Tb and an abundance sensitivity of (6 x 10(-4))-(1.4 x 10(-3)) (trailing and leading masses, respectively) are shown. The mass range (m/z = 125-215) and abundance sensitivity are sufficient for elemental immunoassay with up to 60 distinct available elemental tags. When 500) can be used, which provides >2.4 x 10(8) cps per mg L(-1) of Tb, at (1.5 x 10(-3))-(5.0 x 10(-3)) abundance sensitivity. The real-time simultaneous detection of multiple isotopes from individual 1.8 microm polystyrene beads labeled with lanthanides is shown. A real time single cell 20 antigen expression assay of model cell lines and leukemia patient samples immuno-labeled with lanthanide-tagged antibodies is presented.
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              Single-Cell RNA-Seq Reveals the Transcriptional Landscape and Heterogeneity of Aortic Macrophages in Murine Atherosclerosis

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                Author and article information

                Journal
                Nature Reviews Cardiology
                Nat Rev Cardiol
                Springer Science and Business Media LLC
                1759-5002
                1759-5010
                March 16 2020
                Article
                10.1038/s41569-020-0352-5
                7872210
                32203286
                f68edc07-a40a-4960-afb2-e55cfcf50aa9
                © 2020

                http://www.springer.com/tdm

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