Abstract 1273: Identification of a Novel Subset of T cells in Differentiating Endothelial Progenitor Cells (EPCs) and Facilitating Angiogenesis
Introduction Athymic nude mice which have no functional mature T cells show marked decreased angiogenic capacity compared to normal mice. Early endothelial progenitor cells (EPCs) are known to be a heterogeneous group of cells and EPC colonies are regarded as an important marker of neovascularization and cardiovascular prognosis. However, there have been no direct characterization of EPC colonies and no elucidation of the role of T cells in vasculogenesis and angiogenesis.
Methods & Results We found that CD3+CD31+ T cells, termed angiogenic T cells in our study, form the central cluster of EPC colonies. Without these cells, peripheral mononuclear cells (MNCs) could not form EPC colonies, suggesting that angiogenic T cells are critical in the formation of EPC colonies. Most of these cells expressed CXCR4, a SDF-1 receptor. In addition, angiogenic T cells secreted higher level of angiogenic cytokines such as VEGF, IL-8, and MMP-9. Angiogenic T cells showed superior angiogenic potential compared to other T cell subsets in matrigel tube formation, adhesion, transendo-thelial migration, and vertical invasion assays. Compared with intact whole MNCs, angiogenic T cells-depleted MNCs showed delayed appearance of spindle-shaped EPCs and decreased level of EPC differentiation markers such as Ve-Cadherin and KDR, resulting in decreased angiogenic potency as measured by various assays mentioned earlier. In vivo, a matrigel plug assay showed that angiogenic T cells play an important role in the process of new vessel formation. This was further confirmed in a hindlimb ischemia and myocardial infarction model, where angiogenic T cells showed markedly superior angiogenic potential in blood flow recovery and new capillary formation. In the clinical setting, the level of angiogenic T cells decreased age-dependently and was reduced in patients with coronary artery diseases compared with controls.
Conclusions In conclusion, our study reports for the first time the presence of a novel subpopulation of T cells that form the central cluster of EPC colonies. These cells enhance EPC differentiation and angiogenesis, resulting in improved neovascularization in vivo. These findings suggest that angiogenic T cells could be a good therapeutic target for ischemic heart diseases.