The role of CD27-CD70-mediated T cell co-stimulation in vasculogenesis, arteriogenesis and angiogenesis

K H Simons; Z Aref; H A B Peters; S P Welten; A Y Nossent; J W Jukema; J F Hamming; R Arens; M R de Vries; P H A Quax

doi:10.1016/j.ijcard.2018.02.015

The role of CD27-CD70-mediated T cell co-stimulation in vasculogenesis, arteriogenesis and angiogenesis

Int J Cardiol. 2018 Jun 1:260:184-190. doi: 10.1016/j.ijcard.2018.02.015.

Authors

K H Simons¹, Z Aref¹, H A B Peters¹, S P Welten², A Y Nossent¹, J W Jukema³, J F Hamming⁴, R Arens², M R de Vries¹, P H A Quax⁵

Affiliations

¹ Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
² Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
³ Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
⁴ Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
⁵ Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands; Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: [email protected].

PMID: 29622436
DOI: 10.1016/j.ijcard.2018.02.015

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.

Keywords: Angiogenesis; Arteriogenesis; CD70; Co-stimulation; Neovascularization; T cell.

MeSH terms

Animals
CD27 Ligand / deficiency
CD27 Ligand / physiology*
Hindlimb / blood supply
Hindlimb / diagnostic imaging*
Ischemia / diagnostic imaging*
Ischemia / physiopathology
Laser-Doppler Flowmetry / methods
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Neovascularization, Pathologic / diagnostic imaging*
Neovascularization, Pathologic / physiopathology
Neovascularization, Physiologic / physiology
T-Lymphocytes / physiology*
Tumor Necrosis Factor Receptor Superfamily, Member 7 / deficiency
Tumor Necrosis Factor Receptor Superfamily, Member 7 / physiology*

Substances

CD27 Ligand
Tumor Necrosis Factor Receptor Superfamily, Member 7