Regulation of T cell responses in the developing human fetus.

Although human T cells enter the peripheral lymphoid tissues early during fetal development, the adaptive immune system in the fetus has largely been regarded as functionally immature and unresponsive to stimulation. In this study, we show that depletion of fetal CD4+CD25(high) T regulatory (T(Reg)) cells, which are present at high frequency in fetal lymphoid tissues, results in vigorous T cell proliferation and cytokine production in vitro, even in the absence of exogenous stimulation. Analysis of CD4+ and CD8(+) T cell populations revealed a large subset of cells that expressed the early activation Ag, CD69. We show that this population represents a subset of highly reactive fetal T cells actively suppressed by fetal CD4+CD25(high) T(Reg) cells during development. These findings indicate that fetal T cells are, in the absence of CD4+CD25(high) T(Reg) cells, highly responsive to stimulation and provide evidence for an important role for CD4+CD25(high) T(Reg) cells in controlling T cell responses in utero.