Foxp3high and Foxp3low Treg cells differentially correlate with T helper 1 and natural killer cells in peripheral blood

Abstract Regulatory T (Treg) cells interact with B, natural killer (NK), and dendritic cells in addition to other T cells. In this study, we aimed at determining whether Foxp3+ T cells and subpopulations have any correlation with other lymphocyte subsets and their functions in a systemic immune environment. Peripheral blood was drawn from 22 nonpregnant healthy women. T, B, and NK cell subpopulations were measured by immunophenotype analysis. Intracellular Foxp3, cytokine expression (tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], and interleukin-10 [IL]-10), and NK-cell cytotoxicity were analyzed by flow cytometric analysis. Correlations between Foxp3+ T cells and other immune variables were analyzed under control of age and menstrual phases. Foxp3+ , Foxp3low , and CD4+ Foxp3+ cells significantly correlated with CD4+ CD25+ , CD4+ CD25dim , and CD4+ CD25bright cells. Foxp3+ , Foxp3low , and CD4+ Foxp3+ cells positively correlated with CD3+ and CD3+ CD4+ T cells, but negatively correlated with CD3− CD56+ and CD3− CD56dim NK cells. CD4+ Foxp3high Treg cells were positively correlated with CD3+ CD4+ TNF-α+ ( p = 0.014) and negatively correlated with CD3+ CD8+ IL-10+ T cells ( p = 0.001). The ratio of type 1/2 cytokine-producing CD3+ CD8+ cells demonstrated a positive correlation with CD4+ Foxp3high cells ( p ≤ 0.01). CD8+ Foxp3+ cells were positively correlated with CD3+ CD4+ IL-10+ cells ( p = 0.007) and negatively correlated with CD3+ CD8+ TNF-α+ cells ( p = 0.008). In conclusion, each Foxp3+ Treg cell subpopulation has unique immune interaction, which controls particular subsets of lymphocytes.