What determines Th2 differentiation, in vitro and in vivo?

Immunol Cell Biol. Mar-Apr 2010;88(3):236-9. doi: 10.1038/icb.2010.2. Epub 2010 Feb 16.


We have known since 1991 how to induce naive CD4 T cells to differentiate in vitro into Th2 cells and, over the ensuing years, a comprehensive picture of the molecules involved in this important process has emerged. GATA3 and STAT5 are both essential for in vitro differentiation, stimulating naive cells through a process involving induction, which is T-cell receptor (TCR) dependent but interleukin (IL)-4 independent, and commitment, which is IL-4 dependent. Th2 differentiation in vivo appears more complex. GATA3 and probably STAT5 are required in vivo but, at least for certain helminth infections, the IL-4/IL-4Ra/STAT6 pathway is dispensable. The role of thymic stromal lymphopoietin and of low TCR signal strength and the participation of basophils in establishing a Th2-baising in vivo environment have achieved considerable attention. Here I discuss the major players in Th2 differentiation particularly as they may exert their effects in vivo.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Animals
  • Cell Differentiation / immunology*
  • Cytokines / immunology
  • GATA3 Transcription Factor / immunology
  • Helminthiasis / immunology
  • Helminths / immunology
  • Humans
  • Interleukin-4 / immunology
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Interleukin-4 / immunology
  • STAT5 Transcription Factor / immunology
  • Signal Transduction / immunology
  • Th2 Cells / immunology*


  • Cytokines
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • IL4 protein, human
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-4
  • STAT5 Transcription Factor
  • Interleukin-4
  • thymic stromal lymphopoietin