Stat5 Activation Plays a Critical Role in Th2 Differentiation

• Published in: Immunity (Cambridge, Mass.) Mass.), 2003-11, Vol.19 (5), p.739-748
• Main Authors: Zhu, Jinfang, Cote-Sierra, Javier, Guo, Liying, Paul, William E
• Format: Article
• Language: English
• Subjects: Acquisitions & mergers; Animals; Binding sites; CD4 antigen; Cell Differentiation - physiology; Cell division; Colleges & universities; Cytokines; Cytokines - metabolism; DNA-Binding Proteins - biosynthesis; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; GATA3 Transcription Factor; Gene expression; Infections; Interleukin-4 - metabolism; Mice; Milk Proteins; Receptors, Interleukin-4 - deficiency; Retrovirus; Stat5 protein; STAT5 Transcription Factor; STAT6 Transcription Factor; T cell receptors; Th2 Cells - metabolism; Trans-Activators - biosynthesis; Trans-Activators - deficiency; Trans-Activators - genetics; Trans-Activators - metabolism
• ISSN: 1074-7613; 1097-4180
• 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-4Rα-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.