Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells

Foxp3 plays a key role in CD4(+)CD25(+) T-reg cell function in mice and represents a specific marker for these cells. Despite the strong association between FOXP3 expression and regulatory function in fresh human T cells, little is known about the dynamics of endogenous FOXP3 expression and its relation to the suppressive function in activated human T cells. Here, we addressed the dynamics of FOXP3 expression during human CD4(+) T cell activation by plate-bound anti-CD3 Ab as well as the relationship between its expression and regulatory function at the single-cell level. Our data show that FOXP3 is expressed in a high percentage of activated T cells after in vitro stimulation of human CD4(+)CD25(-) cells. FOXP3 expression is strongly associated with hyporesponsiveness of activated T cells, but is not directly correlated with their suppressive capabilities, as we demonstrate that it is also expressed in activated nonsuppressive T cells. However, in this nonsuppressive T cell population, FOXP3 expression is transient, while it is stably expressed in activated T cells that do display suppressive function, and in natural CD4(+)CD25(++) T-reg cells. These data indicate that expression of endogenous FOXP3, in humans, is not sufficient to induce regulatory T cell activity or to identify T-reg cells.