Dynamic T cell-APC interactions sustain chronic inflammation in atherosclerosis

• Published in: The Journal of clinical investigation Vol. 122; no. 9; pp. 3114 - 3126
• Main Authors: Koltsova, Ekaterina K, Garcia, Zacarias, Chodaczek, Grzegorz, Landau, Michael, McArdle, Sara, Scott, Spencer R, von Vietinghoff, Sibylle, Galkina, Elena, Miller, Yury I, Acton, Scott T, Ley, Klaus
• Format: Journal Article
• Language: English
• Published: United States American Society for Clinical Investigation 01-09-2012
• Subjects: Adventitia - metabolism; Adventitia - pathology; Animals; Antigen presentation; Antigen-Presenting Cells - immunology; Antigen-Presenting Cells - metabolism; Antigen-Presenting Cells - physiology; Aorta - immunology; Aorta - metabolism; Aorta - pathology; Apolipoproteins E - deficiency; Apolipoproteins E - genetics; Atherosclerosis; Atherosclerosis - immunology; Atherosclerosis - pathology; Biomedical research; CD11 Antigens - metabolism; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - physiology; Cell Communication; Cell Movement; Cell Proliferation; Cell Tracking; Cells, Cultured; Coculture Techniques; Coronary vessels; Cytokines; Cytokines - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Dendritic Cells - physiology; Diet, High-Fat; Female; Inflammation; Leukocyte Common Antigens - metabolism; Ligands; Lipids; Lipoproteins, LDL - metabolism; Localization; Lymphatic system; Lymphocytes; Macrophages - immunology; Macrophages - metabolism; Macrophages - physiology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Motility; Plaque, Atherosclerotic - pathology; Tissue Culture Techniques; Vasculitis - immunology; Vasculitis - pathology
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/JCI61758

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.