Cytokine coexpression during human Th1/Th2 cell differentiation: direct evidence for coordinated expression of Th2 cytokines

J Immunol. 2002 Sep 1;169(5):2498-506. doi: 10.4049/jimmunol.169.5.2498.

Abstract

We have developed an in vitro differentiation assay in which human naive CD4(+) cells are driven toward either the Th1 or Th2 phenotype. We have examined the interrelationships among the expression of IL-2, IL-4, IL-5, IL-10, IL-13, GM-CSF, and IFN-gamma in individual cells using intracellular cytokine staining at various times during the differentiation process. We provide direct evidence that the Th2 cytokines IL-4, IL-5, and IL-13, unlike the other cytokines, are regulated by a coordinated mechanism. We also show that IL-10 is expressed by a different subset of cells that is prevalent at early stages of Th2 differentiation, but then diminishes. Additionally we demonstrate that while naive cells can express IL-2 upon activation, they cannot express GM-CSF. Commitment to GM-CSF expression occurs during differentiation in a Th1/Th2 subset-independent manner. Furthermore, we have examined the levels of GATA3, c-Maf, T-bet, and Ets-related molecule during human Th1/Th2 differentiation and suggest that differences in the levels of these critical transcription factors are responsible for commitment toward the Th1 or Th2 lineage.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Cytokines / biosynthesis*
  • DNA-Binding Proteins / biosynthesis
  • DNA-Binding Proteins / genetics
  • GATA3 Transcription Factor
  • Humans
  • Interleukin-10 / biosynthesis
  • Interleukin-13 / biosynthesis
  • Interleukin-5 / biosynthesis
  • Interphase / genetics
  • Interphase / immunology
  • Lymphocyte Activation / genetics
  • Male
  • Protein Isoforms / biosynthesis
  • Protein Isoforms / genetics
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-maf
  • RNA, Messenger / biosynthesis
  • T-Box Domain Proteins
  • Th1 Cells / cytology*
  • Th1 Cells / immunology*
  • Th1 Cells / metabolism
  • Th2 Cells / cytology*
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Trans-Activators / biosynthesis
  • Trans-Activators / genetics
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Substances

  • Cytokines
  • DNA-Binding Proteins
  • ETV5 protein, human
  • GATA3 Transcription Factor
  • GATA3 protein, human
  • Interleukin-13
  • Interleukin-5
  • MAF protein, human
  • Protein Isoforms
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-maf
  • RNA, Messenger
  • T-Box Domain Proteins
  • T-box transcription factor TBX21
  • Trans-Activators
  • Transcription Factors
  • Interleukin-10