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

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.