Document 0160
 DOCN  M95A0160
 TI    Developmental commitment to the Th2 lineage by extinction of IL-12
       signaling.
 DT    9510
 AU    Szabo SJ; Jacobson NG; Dighe AS; Gubler U; Murphy KM; Department of
       Pathology, Washington University School of; Medicine, St. Louis,
       Missouri 63110, USA.
 SO    Immunity. 1995 Jun;2(6):665-75. Unique Identifier : AIDSLINE
       MED/95316722
 AB    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.
 DE    Animal  Base Sequence  Female  Interferon Type II/BIOSYNTHESIS
       Interleukin-12/*ANTAGONISTS & INHIB/*PHYSIOLOGY
       Interleukin-4/PHYSIOLOGY  Lymphocyte Transformation/IMMUNOLOGY  Mice
       Mice, Inbred BALB C  Mice, Transgenic  Molecular Sequence Data
       Protein-Tyrosine Kinase/PHYSIOLOGY  Proteins  Receptors,
       Interleukin/BIOSYNTHESIS  Signal Transduction/*IMMUNOLOGY  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Th1 Cells/IMMUNOLOGY  Th2
       Cells/*IMMUNOLOGY  Trans-Activators/PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).