title: Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution.
abstract: BACKGROUND
  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.
  
  
  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 TEMreceive 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+TEMcells. Reducing the number of TEMcells through a depletion recovery procedure, we show that intravenous TEMactivation 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
  TEMorchestrate the inflammatory response in venous thrombosis affecting thrombus resolution.
authors.affiliation: 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.).
authors.forename: Natascha
authors.initials: N
authors.lastname: Luther
authors.affiliation: 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.).
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shahneh
authors.affiliation: 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.).
authors.forename: Melanie
authors.initials: M
authors.lastname: Brähler
authors.affiliation: 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.).
authors.forename: Franziska
authors.initials: F
authors.lastname: Krebs
authors.affiliation: 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.).
authors.forename: Sven
authors.initials: S
authors.lastname: Jäckel
authors.affiliation: 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.).
authors.forename: Saravanan
authors.initials: S
authors.lastname: Subramaniam
authors.affiliation: 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.).
authors.forename: Christian
authors.initials: C
authors.lastname: Stanger
authors.affiliation: 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.).
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönfelder
authors.affiliation: 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.).
authors.forename: Bettina
authors.initials: B
authors.lastname: Kleis-Fischer
authors.affiliation: 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.).
authors.forename: Christoph
authors.initials: C
authors.lastname: Reinhardt
authors.affiliation: 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.).
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Probst
authors.affiliation: 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.).
authors.forename: Philip
authors.initials: P
authors.lastname: Wenzel
authors.affiliation: 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.).
authors.forename: Katrin
authors.initials: K
authors.lastname: Schäfer
authors.affiliation: 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.
authors.forename: Christian
authors.initials: C
authors.lastname: Becker
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000502:physiology*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D013927:Thrombosis / Q000276:immunology / Q000378:metabolism; D014648:Varicose Veins / Q000276:immunology / Q000378:metabolism*; D020246:Venous Thrombosis / Q000276:immunology / Q000378:metabolism*
keywords: chemokines; cytokines; immune system; lymphocytes; venous thrombosis