Effector T cells and ischemia-induced systemic angiogenesis in the lung

Qiong Zhong, John Jenkins, Aigul Moldobaeva, Franco D'Alessio, Elizabeth M. Wagner

Research output: Contribution to journalArticlepeer-review

Abstract

Lymphocytes have been shown to modulate angiogenesis. Our previous work showed that T regulatory (Treg) cell depletion prevented angiogenesis. In the present study, we sought to examine T-cell populations during lung angiogenesis and subsequent angiostasis. In a mouse model of ischemia-induced systemic angiogenesis in the lung, we examined the time course (0-35 d) of neovascularization and T-cell phenotypes within the lung after left pulmonary artery ligation (LPAL). T cells increased and reached a maximum by 10 days after LPAL and then progressively decreased, suggestive of a modulatory role during the early phase of new vessel growth. Because others have shown IFN-γ to be angiostatic in tumor models, we focused on this effector T-cell cytokine to control the magnitude of angiogenesis. Results showed that IFN-γ protein is secreted at low levels after LPAL and that mice required Treg depletion to see the full effect of effector T cells. Using Foxp3DTR and diphtheria toxin to deplete T regulatory cells, increased numbers of effector T cells (CD8+) and/or increased capacity to secrete the prominent angiostatic cytokine IFN-γ (CD4+) were seen. In vitro culture of mouse systemic and pulmonary microvascular endothelial cells with IFN-γ showed increased endothelial cell apoptosis. CD8-/- mice and IFN-γR-/- mice showed enhanced angiogenesis compared with wild-type mice, confirming that, in this model, IFN-γ limits the extent of systemic neovascularization in the lung.

Original languageEnglish (US)
Pages (from-to)394-401
Number of pages8
JournalAmerican journal of respiratory cell and molecular biology
Volume54
Issue number3
DOIs
StatePublished - Mar 2016

Keywords

  • Angiogenesis
  • Angiostasis
  • IFN-γ
  • Ischemia
  • Regulatory T-cells

ASJC Scopus subject areas

  • Molecular Biology
  • Pulmonary and Respiratory Medicine
  • Clinical Biochemistry
  • Cell Biology

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