Cutting edge:: Decreased accumulation and regulatory function of CD4+CD25high T cells in human STAT 5b deficiency

We show that STAT5b is important for the in vivo accumulation of CD4(+) CD25(high) T cells with regulatory cell function. A patient homozygous for a missense A630P STAT5b mutation displayed immune dysregulation and decreased numbers of CD4(+)CD25(high) T cells. STAT5b(A630P/A630P) CD4(+) CD25(high) T cells had low expression of forkbead box P3 and an impaired ability to suppress the proliferation of or to kill CD4(+) CD25(-) T cells. Expression of CD25, a component of the high-affinity IL-2R, was also reduced in response to IL-2 or after in vitro propagation. The impact of the STAT5b mutan. on was selective in that IL-2-mediated up-regulation of the common gamma-chain cytokine receptor and perforin, and activation-induced expressions of CD154 and IFN-gamma were normal. These results indicate that STAT5b propagates an important IL-2-mediated signal for the in vivo accumulation of functional regulatory T cells.