An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3

J. David Farrar, Wenjun Ouyang, Max Löhning, Mario Assenmacher, Andreas Radbruch, Osami Kanagawa, Kenneth M. Murphy

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

Although interleukin (IL)-12 and IL-4 polarize naive CD4+ T cells toward T helper cell type 1 (Th1) or Th2 phenotypes, it is not known whether cytokines instruct the developmental fate in uncommitted progenitors or select for outgrowth of cells that have stochastically committed to a particular fate. To distinguish these instructive and selective models, we used surface affinity matrix technology to isolate committed progenitors based on cytokine secretion phenotype and developed retroviral-based tagging approaches to directly monitor individual progenitor fate decisions at the clonal and population levels. We observe IL-4-dependent redirection of phenotype in cells that have already committed to a non-IL-4-producing fate, inconsistent with predictions of the selective model. Further, retroviral tagging of naive progenitors with the Th2-specific transcription factor GATA-3 provided direct evidence for instructive differentiation, and no evidence for the selective outgrowth of cells committed to either the Th1 or Th2 fate. These data would seem to exclude selection as an exclusive mechanism in Th1/Th2 differentiation, and support an instructive model of cytokine-driven transcriptional programming of cell fate decisions.

Original languageEnglish (US)
Pages (from-to)643-649
Number of pages7
JournalJournal of Experimental Medicine
Volume193
Issue number5
DOIs
StatePublished - Mar 5 2001

Keywords

  • Cytokine
  • GATA-3
  • Instruction
  • Stochastic
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    David Farrar, J., Ouyang, W., Löhning, M., Assenmacher, M., Radbruch, A., Kanagawa, O., & Murphy, K. M. (2001). An instructive component in T helper cell type 2 (Th2) development mediated by GATA-3. Journal of Experimental Medicine, 193(5), 643-649. https://doi.org/10.1084/jem.193.5.643