血栓
医学
T细胞
炎症
CD8型
趋化因子
静脉血栓形成
血栓形成
免疫学
免疫系统
内科学
作者
Natascha Luther,Fatemeh Zare Shahneh,Melanie Brähler,Franziska Krebs,Sven Jäckel,Saravanan Subramaniam,Christian Stanger,Tanja Schönfelder,Bettina Kleis-Fischer,Carsten Reinhardt,Hans Christian Probst,Philip Wenzel,Katrin Schäfer,Christian Becker
出处
期刊:Circulation Research
[Ovid Technologies (Wolters Kluwer)]
日期:2016-12-09
卷期号:119 (12): 1286-1295
被引量:54
标识
DOI:10.1161/circresaha.116.309301
摘要
Rationale: Immune cells play an important role during the generation and resolution of thrombosis. T cells are powerful regulators of immune and nonimmune cell function, however, their role in sterile inflammation in venous thrombosis has not been systematically examined. Objective: This study investigated the recruitment, activation, and inflammatory activity of T cells in deep vein thrombosis and its consequences for venous thrombus resolution. Methods and Results: CD4 + and CD8 + T cells infiltrate the thrombus and vein wall rapidly on deep vein thrombosis induction and remain in the tissue throughout the thrombus resolution. In the vein wall, recruited T cells largely consist of effector-memory T (T EM ) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis–recruited T EM receive an immediate antigen-independent activation and produce IFN-γ (interferon) in situ. Mapping inflammatory conditions in the thrombotic vein, we identify a set of deep vein thrombosis upregulated cytokines and chemokines that synergize to induce antigen-independent IFN-γ production in CD4 + and CD8 + T EM cells. Reducing the number of T EM cells through a depletion recovery procedure, we show that intravenous T EM activation determines neutrophil and monocyte recruitment and delays thrombus neovascularization and resolution. Examining T-cell recruitment in human venous stasis, we show that superficial varicose veins preferentially contain activated memory T cells. Conclusions: T EM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution.
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