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CUTTING EDGE |
* Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305;
Department of Pediatrics, Oregon Health and Sciences University, Portland, Oregon 97239; and
Department of Endocrinology and
Department of Pulmonology, Hospital General de Niños Ricardo Gutiérrez, Buenos Aires, Argentina
We show that STAT5b is important for the in vivo accumulation of CD4+CD25high T cells with regulatory cell function. A patient homozygous for a missense A630P STAT5b mutation displayed immune dysregulation and decreased numbers of CD4+CD25high T cells. STAT5bA630P/A630P CD4+CD25high 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 
-chain cytokine receptor and perforin, and activation-induced expressions of CD154 and IFN- were normal. These results indicate that STAT5b propagates an important IL-2-mediated signal for the in vivo accumulation of functional regulatory T cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by National Institutes of Health Grant K08 AI057961-01 (to A.C.C), an American Society of Hematology Fellow Basic Science Award (to A.C.C), the Jeffrey Modell Center for Primary Immunodeficiency (to D.B.L), and a Berry Fellowship in Children’s Health (to K.C.N.).
2 Address correspondence and reprint requests to Dr. David B. Lewis, Division of Immunology and Transplantation Biology, Center for Clinical Sciences Research Building, Room 2115b, Stanford University School of Medicine, 269 Campus Drive, Stanford, CA 94305-5164. E-mail address: dblewis{at}stanford.edu
3 Abbreviations used in this paper: Treg, CD4+CD25high regulatory T cell; AC, allophycocyanin; Foxp3, forkhead box P3; c, common chain; control (IS), control treated with immunosuppressive glucocorticoid therapy; SEB, Staphylococcus aureus enterotoxin B; wt, wild type.
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