['CD4(+)CD25(+) regulatory T lymphocytes (Treg) have been initially shown to prevent organ-specific autoimmunity. It is now accepted that Treg homeostasis depends in part on the peripheral conversion of naïve CD4(+)CD25(-) T cells. This conversion implicates acquisition of the Treg-specific markers, forkhead winged helix protein 3 (Foxp3), after CD28 costimulation. Because natural killer cells (NK) are critical for efficient cytotoxic T-cell priming and TH1 polarization, we investigated their role in Foxp3 induction in CD4(+) T lymphocytes.', 'Human CD4(+)CD25(-) T lymphocytes were activated in vitro by CD28 costimulation in the presence of interleukin-2-activated NK. Three days after initial activation, Foxp3 protein and RNA expression were determined by flow cytometry and reverse transcription polymerase chain reaction. In vivo influence of activated NK on Foxp3 expression was studied in an adoptive transfer model of CD45.2(+) CD4(+)CD25(-) lymphocytes into CD45.1(+) mice.', 'Interleukin-2-activated NK decreased Treg conversion of adoptively transferred murine CD4(+)CD25(-) T cells in vivo. Likewise, human-activated NK, but not resting NK, decreased CD28-driven Foxp3 expression in CD4(+)CD25(-) T lymphocytes, while at the same time increasing proliferation and interferon-gamma (IFN-gamma) production. Neutralization of IFN-gamma partially restored Treg conversion and prevented TH1 polarization after CD28 costimulation.'] Do natural killer cells prevent CD28-mediated Foxp3 transcription in CD4+CD25- T lymphocytes?