In:
Circulation Research, Ovid Technologies (Wolters Kluwer Health), Vol. 119, No. 12 ( 2016-12-09), p. 1286-1295
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0009-7330
,
1524-4571
DOI:
10.1161/CIRCRESAHA.116.309301
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2016
detail.hit.zdb_id:
1467838-X
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