title: 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.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology (LIAI), La Jolla, California 92037, USA.
authors.forename: Ekaterina K
authors.initials: EK
authors.lastname: Koltsova
authors.forename: Zacarias
authors.initials: Z
authors.lastname: Garcia
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Chodaczek
authors.forename: Michael
authors.initials: M
authors.lastname: Landau
authors.forename: Sara
authors.initials: S
authors.lastname: McArdle
authors.forename: Spencer R
authors.initials: SR
authors.lastname: Scott
authors.forename: Sibylle
authors.initials: S
authors.lastname: von Vietinghoff
authors.forename: Elena
authors.initials: E
authors.lastname: Galkina
authors.forename: Yury I
authors.initials: YI
authors.lastname: Miller
authors.forename: Scott T
authors.initials: ST
authors.lastname: Acton
authors.forename: Klaus
authors.initials: K
authors.lastname: Ley
mesh_terms: D063194:Adventitia / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D001011:Aorta / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000276:immunology / Q000473:pathology*; D018845:CD11 Antigens / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000502:physiology; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D058948:Cell Tracking; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D059305:Diet, High-Fat; D005260:Female; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D058226:Plaque, Atherosclerotic / Q000473:pathology; D046509:Tissue Culture Techniques; D014657:Vasculitis / Q000276:immunology / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D018845:CD11 Antigens; D016207:Cytokines; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse