Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.
Circ Res
; 119(12): 1286-1295, 2016 Dec 09.
Article
en En
| MEDLINE
| ID: mdl-27707800
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 ANDRESULTS:
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.Palabras clave
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Bases de datos:
MEDLINE
Asunto principal:
Várices
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Linfocitos T CD4-Positivos
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Linfocitos T CD8-positivos
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Trombosis de la Vena
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Inmunidad Innata
Límite:
Animals
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Humans
Idioma:
En
Revista:
Circ Res
Año:
2016
Tipo del documento:
Article