Developmental commitment to the Th2 lineage by extinction of IL-12 signaling

Immunity. 1995 Jun;2(6):665-75. doi: 10.1016/1074-7613(95)90011-x.


Developmental-commitment to Th1 or Th2 responses critically influences host susceptibility to particular pathogens. We describe a novel mechanism governing stable commitment to Th2 differentiation. Naive T cells develop strongly polarized Th1 and Th2 profiles by 7 days after activation. However, commitment of these developing cells differs substantially. Although IL-4 reverses early Th1 differentiation, IL-12 cannot reverse early Th2 differentiation. Th1 reversibility results from maintenance of IL-4 signal transduction, whereas Th2 commitment results from rapid loss of IL-12 signaling. The IL-12 signaling defect in Th2 cells results in failure to phosphorylate Jak2, Stat3, and Stat4. Since Th2 cells express the mRNA for the cloned murine IL-12 receptor beta subunit, the signaling defect may involve expression or function of unidentified receptor components. The rapid extinction of IL-12 signaling in Th2 cells provides a demonstration of a mechanism for the stable commitment to a T helper phenotype.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Base Sequence
  • Female
  • Interferon-gamma / biosynthesis
  • Interleukin-12 / antagonists & inhibitors*
  • Interleukin-12 / physiology*
  • Interleukin-4 / physiology
  • Janus Kinase 2
  • Lymphocyte Activation / immunology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Transgenic
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases / physiology
  • Proteins
  • Proto-Oncogene Proteins*
  • Receptors, Interleukin / biosynthesis
  • Receptors, Interleukin-12
  • Signal Transduction / immunology*
  • TYK2 Kinase
  • Th1 Cells / immunology
  • Th2 Cells / immunology*
  • Trans-Activators / physiology


  • Proteins
  • Proto-Oncogene Proteins
  • Receptors, Interleukin
  • Receptors, Interleukin-12
  • Trans-Activators
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • Protein-Tyrosine Kinases
  • Jak2 protein, mouse
  • Janus Kinase 2
  • TYK2 Kinase
  • Tyk2 protein, mouse