Autoimmune Processes Linked to Formation of Atherosclerotic Plaques

Results obtained by live-cell imaging studies of explanted aortas suggest that the buildup of atherosclerotic plaques may be linked to previously unrecognized autoimmune processes.

Investigators at the La Jolla Institute for Allergy and Immunology (CA, USA) developed a live-cell imaging technique to study explanted aortas in order to compare the behavior and role of APCs (antigen processing cells) in normal and atherosclerotic mice.

They reported in the August 13, 2012, online edition of the Journal of Clinical Investigation 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 interacted extensively with CD4+ T cells in the aorta, leading to cell activation and proliferation as well as to the secretion of IFN-gamma (interferon-gamma) and TNF-alpha (tumor necrosis factor-alpha). These cytokines enhanced uptake of oxidized and minimally modified LDL (low-density lipoprotein) by macrophages that had been attracted to sites of inflammation in the arterial wall. Thus, antigen presentation by APCs to CD4+ T cells in the arterial wall caused local T cell activation and production of proinflammatory cytokines, which promoted atherosclerosis by maintaining chronic inflammation and inducing foam cell formation.

"The thing that excites me most about this finding is that these immune cells appear to have "memory" of the molecule brought forth by the antigen-presenting cells," said senior author Dr. Klaus Ley, professor of autoimmune research and inflammation biology at the La Jolla Institute for Allergy and Immunology. "Immune memory is the underlying basis of successful vaccines. This means that conceptually it becomes possible to consider the development of a vaccine for heart disease".

"The T cells talk to the antigen-presenting cells and, in response, make cytokines that launch an attack. This is what makes the inflammation in the vessel wall persistent," said Dr. Ley. "Inflammatory cells join fat and cholesterol to form artery-clogging plaque that can eventually block blood flow, leading to a heart attack. It was not previously known that antigen-experienced T cells existed in the vessel wall. This experiment makes me now believe that it may be possible to build a vaccine for heart disease".

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La Jolla Institute for Allergy and Immunology