Depletion of CD4 and CD8 positive T Cells impairs venous thrombus resolution in mice
JournalInternational Journal of Molecular Sciences
MetadataShow full item record
AbstractResolution of deep venous thrombosis involves coordinated inflammatory processes. T cells regulate inflammation in vivo and modulate vascular remodeling in other settings, but their role in venous thrombus resolution remains undefined. To determine the role of T cells in venous thrombus resolution in vivo, stasis induced thrombi were created by vena cava ligation in outbred CD?1 mice. CD4 and CD8 positive T cells, as determined by flow cytometry, were present in thrombi both during thrombus formation and resolution. Depletion of the CD4 and CD8 positive T cells by antibody treatment selectively impaired thrombus resolution compared to animals treated with isotype control antibodies, without an effect on venous thrombus formation. Quantitation of intra-thrombus macrophage numbers, fibrinolytic marker expression, and gelatinolytic activity by zymography revealed that T cell depletion decreased the number of macrophages, reduced the expression of fibrinolytic marker urokinase plasminogen activator (uPA), and decreased the activity of matrix metalloprotinease?9 (MMP?9). These data implicate CD4 and CD8 positive T cells in functionally contributing to venous thrombus resolution, thus representing a potential therapeutic target, but also underscoring potential risks involved in T cell depletion used clinically for solid organ and hematopoietic transplantation procedures. Copyright 2020 by the authors.
SponsorsThis work was supported by National Institutes of Health, National Heart, Lung, and Blood Institute grant R01 HL083917 (to R.S.), and also in part by VA Maryland Health Care System Merit award I01 BX001921 (to T.M.A.).
Peripheral vascular disease
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85080888181&doi=10.3390%2fijms21051650&partnerID=40&md5=d38805b3ee5a2c15cc7738238cebf026; http://hdl.handle.net/10713/12235
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