Significant Differences in Antigen-Induced Transendothelial Migration of Human CD8 and CD4 T Effector Memory Cells

Manes, Thomas D.; Pober, Jordan S.

doi:10.1161/atvbaha.116.308039

Cited by 14 publications

(17 citation statements)

References 39 publications

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“…Atherosclerosis is a complex inflammatory disease of medium and large-sized arteries, in which three cellular types are mainly involved, including endothelial cells, macrophages, and smooth muscle cells 25 – 27 . The pathophysiologic mechanisms by which nicotine promotes vascular diseases particularly atherosclerosis is manifold and complex.…”

Section: Discussionmentioning

confidence: 99%

Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis

et al. 2018

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Cigarette smoking is a major risk factor for atherosclerosis and other cardiovascular diseases. Increasing evidence has demonstrated that nicotine impairs the cardiovascular system by targeting vascular endothelial cells, but the underlying mechanisms remain obscure. It is known that cell death and inflammation are crucial processes leading to atherosclerosis. We proposed that pyroptosis may be implicated in nicotine-induced atherosclerosis and therefore conducted the present study. We found that nicotine resulted in larger atherosclerotic plaques and secretion of inflammatory cytokines in ApoE−/− mice fed with a high-fat diet (HFD). Treatment of human aortic endothelial cells (HAECs) with nicotine resulted in NLRP3-ASC inflammasome activation and pyroptosis, as evidenced by cleavage of caspase-1, production of downstream interleukin (IL)-1β and IL-18, and elevation of LDH activity and increase of propidium iodide (PI) positive cells, which were all inhibited by caspase-1 inhibitor. Moreover, silencing NLRP3 or ASC by small interfering RNA efficiently suppressed nicotine-induced caspase-1 cleavage, IL-18 and IL-1β production, and pyroptosis in HAECs. Further experiments revealed that the nicotine-NLRP3-ASC-pyroptosis pathway was activated by reactive oxygen species (ROS), since ROS scavenger (N-acetyl-cysteine, NAC) prevented endothelial cell pyroptosis. We conclude that pyroptosis is likely a cellular mechanism for the pro-atherosclerotic property of nicotine and stimulation of ROS to activate NLRP3 inflammasome is a signaling mechanism for nicotine-induced pyroptosis.

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Section: Discussionmentioning

confidence: 99%

Nicotine promotes atherosclerosis via ROS-NLRP3-mediated endothelial cell pyroptosis

et al. 2018

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“…Cell culture experiments using superantigen have revealed that both CD4+ and CD8+ T EM that recognize antigens on the apical surface of human microvascular ECs are induced to transmigrate through the EC barrier ( 66 ). Morphologically, the initial T cell response to antigen recognition on ECs appears similar to that which occurs during antigen presentation by professional APCs.…”

Section: Antigen Presentation By Ecsmentioning

confidence: 99%

“…During TCR-triggered transendothelial migration, CD4+ T EM discharge granules, releasing granzyme A, the proteolytic activity of which is required for effective transmigration ( 67 ). In contrast, CD8+ T EM transits through the EC monolayer without discharging their granules, which contain granzyme B and perforin in addition to granzyme A ( 66 ). The basis for this difference in granule release is unknown but protects EC from lysis.…”

Section: Antigen Presentation By Ecsmentioning

confidence: 99%

Antigen Presentation by Vascular Cells

et al. 2017

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Antigen presentation by cells of the vessel wall may initiate rapid and localized memory immune responses in peripheral tissues. Peptide antigens displayed on major histocompatibility complex (MHC) molecules on the surface of endothelial cells (ECs) can be recognized by T cell receptors on circulating effector memory T cells (TEM), triggering both transendothelial migration and activation. The array of co-stimulatory receptors, adhesion molecules, and cytokines expressed by ECs serves to modulate T cell activation responses. While the effects of these interactions vary among species, vascular beds, and vascular segments within the same tissue, they are capable of triggering allograft rejection without direct involvement of professional antigen-presenting cells and may play a similar role in host defense against infections and in autoimmunity. Once across the endothelium, extravasating TEM then contact mural cells of the vessel wall, including pericytes or vascular smooth muscle cells, which may also present antigens and provide signals that further regulate T cell responses. Collectively, these interactions provide an unexplored opportunity in which targeting of vascular cells can be used to modulate immune responses. In organ transplantation, targeting ECs with siRNA to reduce expression of MHC molecules may additionally mitigate perioperative injuries by preformed alloantibodies, further reducing the risk of graft rejection. Similarly, genetic manipulation of vascular cells to minimize antigen-dependent responses can be used to increase perfusion of tissue engineered organs without triggering rejection.

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“…[4][5][6] This, in addition to the accumulation of cholesterol and smooth muscle cells (SMCs) in the intima, leads to the transformation of monocytes into foam cells, which consume dead cells and lipids. [7][8][9] The atherogenic process involves multiple cell types, that is, endothelial cells (ECs), 10 SMCs, 11 immune cells, 12 and stem/progenitor cells, 13 in which levels of both intracellular and extracellular reactive oxygen and nitrogen species play a fundamental role in vascular cell homoeostasis and eventually affects the development of atherosclerosis.…”

mentioning

confidence: 99%