Stat5 activation plays a critical role in Th2 differentiation

Immunity. 2003 Nov;19(5):739-48. doi: 10.1016/s1074-7613(03)00292-9.


Upon TCR engagement, naive CD4 T cells differentiate toward the Th1 or Th2 phenotype. IL-4, acting through Stat6, plays a major role in Th2 differentiation; IL-2 has also been reported to be essential. Here, we report that retroviral (RV)-mediated expression of a constitutively active Stat5A mutant (STAT5A1*6) can fully restore IL-4 production when naive CD4 T cells are primed in the absence of IL-2. Furthermore, STAT5A1*6 expression causes Th2 differentiation in the absence of IL-4 or in Stat6- or IL-4Ralpha-deficient cells. Infection with STAT5A1*6-NGFR-RV does not enhance GATA-3 expression. STAT5A1*6-NGFR-RV and GATA-3-GFP-RV each render the Il4 gene accessible, but the sites of restriction enzyme accessibility are different. Stat5A binds to HSII and HSIII sites of the Il4 gene. Coinfection with STAT5A1*6-NGFR-RV and GATA-3-GFP-RV results in optimal Th2 priming.

MeSH terms

  • Animals
  • Cell Differentiation / physiology*
  • Cytokines / metabolism
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • GATA3 Transcription Factor
  • Interleukin-4 / metabolism
  • Mice
  • Milk Proteins*
  • Receptors, Interleukin-4 / deficiency
  • STAT5 Transcription Factor
  • STAT6 Transcription Factor
  • Th2 Cells / metabolism*
  • Trans-Activators / biosynthesis
  • Trans-Activators / deficiency
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*


  • Cytokines
  • DNA-Binding Proteins
  • GATA3 Transcription Factor
  • Gata3 protein, mouse
  • Milk Proteins
  • Receptors, Interleukin-4
  • STAT5 Transcription Factor
  • STAT6 Transcription Factor
  • Stat5a protein, mouse
  • Stat6 protein, mouse
  • Trans-Activators
  • Interleukin-4