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

Susanne J. Szabo, Nile G. Jacobson, Anand S. Dighe, Uell Gubler, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

413 Scopus citations

Abstract

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 β 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.

Original languageEnglish
Pages (from-to)665-675
Number of pages11
JournalImmunity
Volume2
Issue number6
DOIs
StatePublished - Jun 1995

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