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J Clin Invest. 2012 Sep;122(9):3114-26. doi: 10.1172/JCI61758. Epub 2012 Aug 13.

Dynamic T cell-APC interactions sustain chronic inflammation in atherosclerosis.

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1
Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California 92037, USA.

Abstract

Atherosclerosis is a chronic inflammatory disease of large and medium-sized arteries characterized by leukocyte accumulation in the vessel wall. Both innate and adaptive immune responses contribute to atherogenesis, but the identity of atherosclerosis-relevant antigens and the role of antigen presentation in this disease remain poorly characterized. We developed live-cell imaging of explanted aortas to compare the behavior and role of APCs in normal and atherosclerotic mice. We found that CD4+ T cells were capable of interacting with fluorescently labeled (CD11c-YFP+) APCs in the aortic wall in the presence, but not the absence, of cognate antigen. In atherosclerosis-prone Apoe-/-CD11c-YFP+ mice, APCs extensively interacted with CD4+ T cells in the aorta, leading to cell activation and proliferation as well as secretion of IFN-γ and TNF-α. These cytokines enhanced uptake of oxidized and minimally modified LDL by macrophages. We conclude that antigen presentation by APCs to CD4+ T cells in the arterial wall causes local T cell activation and production of proinflammatory cytokines, which promote atherosclerosis by maintaining chronic inflammation and inducing foam cell formation.

PMID:
22886300
PMCID:
PMC3428082
DOI:
10.1172/JCI61758
[Indexed for MEDLINE]
Free PMC Article
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