Cutting edge: Decreased accumulation and regulatory function of CD4+ CD25(high) T cells in human STAT5b 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 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 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.
Cohen
Aileen C
AC
Department of Pediatrics, Stanford University School of Medicine, Stanford, California 94305, USA.
Nadeau
Kari C
KC
Tu
Wenwei
W
Hwa
Vivian
V
Dionis
Kira
K
Bezrodnik
Liliana
L
Teper
Alejandro
A
Gaillard
Maria
M
Heinrich
Juan
J
Krensky
Alan M
AM
Rosenfeld
Ron G
RG
Lewis
David B
DB
D000328:Adult; D000409:Alanine / Q000235:genetics / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D009154:Mutation / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000378:metabolism*; D050799:STAT5 Transcription Factor / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; C494095:STAT5B protein, human; D000409:Alanine