Abstract:
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 (TEM) cells. Using T-cell receptor transgenic reporter mice, we demonstrate that deep vein thrombosis-recruited TEM 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+ TEM cells. Reducing the number of TEM cells through a depletion recovery procedure, we show that intravenous TEM 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:TEM orchestrate the inflammatory response in venous thrombosis affecting thrombus resolution.
journal_name
Circ Resjournal_title
Circulation researchauthors
Luther N,Shahneh F,Brähler M,Krebs F,Jäckel S,Subramaniam S,Stanger C,Schönfelder T,Kleis-Fischer B,Reinhardt C,Probst HC,Wenzel P,Schäfer K,Becker Cdoi
10.1161/CIRCRESAHA.116.309301subject
Has Abstractpub_date
2016-12-09 00:00:00pages
1286-1295issue
12eissn
0009-7330issn
1524-4571pii
CIRCRESAHA.116.309301journal_volume
119pub_type
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