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Circ Res. 2016 Dec 9;119(12):1286-1295. Epub 2016 Oct 5.

Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.

Author information

1
From the Department of Dermatology (N.L., F.S., M.B., F.K., C.S., B.K.-F., C.B.), Center for Thrombosis and Hemostasis (CTH) (S.J., S.S., T.S., C.R., P.W., C.B.), Institute for Immunology (H.C.P.), and Center for Cardiology, Cardiology I, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Germany (P.W., K.S.).
2
From the Department of Dermatology (N.L., F.S., M.B., F.K., C.S., B.K.-F., C.B.), Center for Thrombosis and Hemostasis (CTH) (S.J., S.S., T.S., C.R., P.W., C.B.), Institute for Immunology (H.C.P.), and Center for Cardiology, Cardiology I, University Medical Center Mainz, Johannes Gutenberg-University Mainz, Germany (P.W., K.S.). christian.becker@unimedizin-mainz.de.

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.

KEYWORDS:

chemokines; cytokines; immune system; lymphocytes; venous thrombosis

PMID:
27707800
DOI:
10.1161/CIRCRESAHA.116.309301
[Indexed for MEDLINE]

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