Dynamic T cell–APC interactions sustain chronic inflammation in atherosclerosis
Ekaterina K. Koltsova, … , Scott T. Acton, Klaus Ley
Ekaterina K. Koltsova, … , Scott T. Acton, Klaus Ley
Published August 13, 2012
Citation Information: J Clin Invest. 2012;122(9):3114-3126. https://doi.org/10.1172/JCI61758.
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Research Article Cardiology

Dynamic T cell–APC interactions sustain chronic inflammation in atherosclerosis

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.

Authors

Ekaterina K. Koltsova, Zacarias Garcia, Grzegorz Chodaczek, Michael Landau, Sara McArdle, Spencer R. Scott, Sibylle von Vietinghoff, Elena Galkina, Yury I. Miller, Scott T. Acton, Klaus Ley

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Figure 1

Myeloid cells in aortic plaque and adventitia.

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Myeloid cells in aortic plaque and adventitia. (A) Live CD45+ cells from...
(A) Live CD45+ cells from aortas of Apoe–/– mice fed CD or WD for 12 weeks were stained for CD11b and CD11c. Numbers indicate percentage in each quadrant. (B) Localization of CD11b+CD11c– (green), CD11b+CD11c+ (yellow), and CD11b–CD11c+ (red) cells in aortic roots of WD-fed Apoe–/– mice, shown by immunofluorescence. Dotted white lines indicate border of lamina muscularis. L, lumen; P, plaque; A, adventitia. Representative images from at least 3 independent experiments. (C) Examples of CD11b+CD11c–, CD11b+CD11c+, and CD11b–CD11c+ cells in the adventitia enlarged from boxed regions in B. Localization of CD11c-YFP+ cells (green) in normal B6 (D) and in atherosclerotic Apoe–/– (E) mouse aorta. Blue, second harmonic; brown, autofluorescence. Scale bars: 100 μm (B); 2 μm (C, left); 5 μm (C, middle and right); 150 μm (D and E).