1. The role of CD27-CD70-mediated T cell co-stimulation in vasculogenesis, arteriogenesis and angiogenesis.
- Author
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Simons KH, Aref Z, Peters HAB, Welten SP, Nossent AY, Jukema JW, Hamming JF, Arens R, de Vries MR, and Quax PHA
- Subjects
- Animals, CD27 Ligand deficiency, Hindlimb blood supply, Ischemia physiopathology, Laser-Doppler Flowmetry methods, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neovascularization, Pathologic physiopathology, Neovascularization, Physiologic physiology, Tumor Necrosis Factor Receptor Superfamily, Member 7 deficiency, CD27 Ligand physiology, Hindlimb diagnostic imaging, Ischemia diagnostic imaging, Neovascularization, Pathologic diagnostic imaging, T-Lymphocytes physiology, Tumor Necrosis Factor Receptor Superfamily, Member 7 physiology
- Abstract
Background: T cells have a distinctive role in neovascularization, which consists of arteriogenesis and angiogenesis under pathological conditions and vasculogenesis under physiological conditions. However, the role of co-stimulation in T cell activation in neovascularization has yet to be established. The aim of this study was to investigate the role T cell co-stimulation and inhibition in angiogenesis, arteriogenesis and vasculogenesis., Methods and Results: Hind limb ischemia was induced by double ligation of the left femoral artery in mice and blood flow recovery was measured with Laser Doppler Perfusion Imaging in control, CD70
-/- , CD80/86-/- , CD70/80/86-/- and CTLA4+/- mice. Blood flow recovery was significantly impaired in mice lacking CD70 compared to control mice, but was similar in CD80/86-/- , CTLA4+/- and control mice. Mice lacking CD70 showed impaired vasculogenesis, since the number of pre-existing collaterals was reduced as observed in the pia mater compared to control mice. In vitro an impaired capability of vascular smooth muscle cells (VSMC) to activate T cells was observed in VSMC lacking CD70. Furthermore, CD70-/- , CD80/86-/- and CD70/80/86-/- mice showed reduced angiogenesis in the soleus muscle 10 days after ligation. Arteriogenesis was also decreased in CD70-/- compared to control mice 10 and 28 days after surgery., Conclusions: The present study is the first to describe an important role for T cell activation via co-stimulation in angiogenesis, arteriogenesis and vasculogenesis, where the CD27-CD70 T cell co-stimulation pathway appears to be the most important co-stimulation pathway in pre-existing collateral formation and post-ischemic blood flow recovery, by arteriogenesis and angiogenesis., (Copyright © 2018 Elsevier B.V. All rights reserved.)- Published
- 2018
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