Cutting edge: Decreased accumulation and regulatory function of CD4 +CD25 high T cells in human STAT5b deficiency

Abstract

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 forkhead 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 mutation was selective in that IL-2-mediated up-regulation of the common γ-chain cytokine receptor and perform, and activation-induced expressions of CD154 and IFN-γ were normal. These results indicate that STAT5b propagates an important IL-2-mediated signal for the in vivo accumulation of functional regulatory T cells. Copyright © 2006 by The American Association of Immunologists, Inc.