Association Between Circulating Early Endothelial Progenitors and CD4+CD25+ Regulatory T Cells: A Possible Cross-talk between Immunity and Angiogenesis?

Abstract

Regulatory T-cells (Treg) are a recently defined subset of CD4+ cells that can suppress inflammation and induce tolerance. Phenotypically, T-regs are characterized by a high level of expression of the IL-2 receptor alpha chain, CD25. Endothelial progenitor cells (EPCs) can transform into mature endothelial cells and promote vessel formation by inducing postnatal angiogenesis and vasculogenesis. Herein, we tested the hypothesis that an association exists between circulating EPC and Tregs that could potentially allude to cross talk between immunity and angiogenesis. Peripheral blood mononuclear cells were isolated by Ficoll density-gradient centrifugation from 28 subjects. Circulating number of EPCs at various developmental stages (CD133+CD34+, CD133+VEGFR2+, CD34+VEGFR2+), total CD4+ and Treg CD4+CD25^high) numbers were determined by FACS analysis. We found a positive correlation between early progenitor cell (CD133+CD34+) number and Tregs, but no correlation between differentiated EPCs and Tregs, or between CD4+ and any of the EPCs sampled. Early EPCs (CD133+CD34+) did not correlate with CD34+/KDR or with CD133/KDR cells. Circulating numbers of early but not ‘mature’ EPC correlate with Tregs but not CD4 numbers. This finding may suggest a novel role for Tregs in promoting EPC recruitment or delaying EPC maturation.