2012年8月24日 讯 /生物谷BIOON/ --一在动脉粥样硬化小鼠模型中同源抗原的存在下,CD4+T细胞能与抗原递呈细胞(APCs)相互作用,从而导致细胞的活化和增殖以及促炎性细胞因子的分泌,这项最新实验性的研究发表在Journal of Clinical Investigation杂志上。
加利福尼亚州拉霍亚研究所过敏和免疫学医学博士Ekaterina K. Koltsova和他的同事运用主动脉用活细胞成像技术比较了抗原递呈细胞在正常以及动脉粥样硬化小鼠中的生物学行为和作用。
研究人员发现,在同源抗原存在的情况下,CD4+T细胞能与APCs在主动脉壁中发生的互动,而同源抗原不存在的情况下,两者之间并不发生联系。在易发生动脉粥样硬化的小鼠中,APCs与主动脉中的CD4+T细胞发生联系后导致细胞的活化和增殖,同时也促进细胞因子(干扰素-γ,肿瘤坏死因子-α)的分泌。
研究结论是APCs抗原递呈给动脉壁中的CD4+T细胞,造成局部T细胞活化和炎性细胞因子的生产,从而通过慢性炎症、诱导泡沫细胞的形成促进动脉粥样硬化。(生物谷:Bioon.com)
编译自:T cells key in atherosclerosis-linked inflammation
doi:10.1172/JCI61758
PMC:
PMID:
Dynamic T cell–APC interactions sustain chronic inflammation in atherosclerosis
Ekaterina K. Koltsova1, Zacarias Garcia1, Grzegorz Chodaczek1, Michael Landau2, Sara McArdle1,3, Spencer R. Scott1, Sibylle von Vietinghoff1,4, Elena Galkina5, Yury I. Miller6, Scott T. Acton2 and Klaus Ley1
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.