Impaired development of human Th1 cells in patients with deficient expression of STAT4

Hua Chen Chang, Ling Han, Ritobrata Goswami, Evelyn T. Nguyen, David Pelloso, Michael Robertson, Mark Kaplan

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

IL-12 activates STAT4, which is a critical regulator of inflammation and T helper type I (Th1) lineage development in murine systems. The requirement for STAT4 in the generation of human Th1 cells has not been examined thoroughly. Compared with control Th1 cultures, expression of the Th1 genes IFNγ, IL-12Rβ2, and TNFα is greatly reduced in Th1 cultures of CD4 T cells isolated from lymphoma patients after autologous stem cell transplantation who have acquired STAT4 deficiency. Moreover, IL-4 and IL-5 production is increased in patient Th1 cultures though there are no defects in the development of Th2 cells. Reconstitution of STAT4 in patient T cells allowed recovery of IFNγ and IL-12Rβ2 expression, whereas ectopic expression of IL-12Rβ2 did not rescue STAT4 expression, and increased IFNγ production only to levels intermediate between control and patient samples. These results demonstrate that, as in murine systems, STAT4 is required for optimal human Th1 lineage development.

Original languageEnglish
Pages (from-to)5887-5890
Number of pages4
JournalBlood
Volume113
Issue number23
DOIs
StatePublished - 2009

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Th1 Cells
T-cells
Human Development
Cell culture
Interleukin-5
Interleukin-12
Stem cells
Interleukin-4
Genes
Recovery
Th2 Cells
Defects
T-Cell Lymphoma
Stem Cell Transplantation
Inflammation
T-Lymphocytes
Gene Expression

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Impaired development of human Th1 cells in patients with deficient expression of STAT4. / Chang, Hua Chen; Han, Ling; Goswami, Ritobrata; Nguyen, Evelyn T.; Pelloso, David; Robertson, Michael; Kaplan, Mark.

In: Blood, Vol. 113, No. 23, 2009, p. 5887-5890.

Research output: Contribution to journalArticle

Chang, Hua Chen ; Han, Ling ; Goswami, Ritobrata ; Nguyen, Evelyn T. ; Pelloso, David ; Robertson, Michael ; Kaplan, Mark. / Impaired development of human Th1 cells in patients with deficient expression of STAT4. In: Blood. 2009 ; Vol. 113, No. 23. pp. 5887-5890.
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AU - Robertson, Michael

AU - Kaplan, Mark

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