A common factor regulates both Th1- and Th2-specific cytokine gene expression

EMBO J. 1994 Feb 1;13(3):625-33.

Abstract

Murine T helper cell clones are classified into two distinct subsets, T helper 1 (Th1) and T helper 2 (Th2), on the basis of cytokine secretion patterns. Th1 clones produce interleukin-2 (IL-2), tumor necrosis factor-beta (TNF-beta) and interferon-gamma (IFN-gamma), while Th2 clones produce IL-4, IL-5, IL-6 and IL-10. These subsets differentially promote delayed-type hypersensitivity or antibody responses, respectively. The nuclear factor NF-AT is induced in Th1 clones stimulated through the T cell receptor-CD3 complex, and is required for IL-2 gene induction. The NF-AT complex consists of two components: NF-ATp, which pre-exists in the cytosol and whose appearance in the nucleus is induced by an increase of intracellular calcium, and a nuclear AP-1 component whose induction is dependent upon activation of protein kinase C (PKC). Here we report that the induction of the Th2-specific IL-4 gene in an activated Th2 clone involves an NF-AT complex that consists only of NF-ATp, and not the AP-1 component. On the basis of binding experiments we show that this 'AP-1-less' NF-AT complex is specific for the IL-4 promoter and does not reflect the inability of activated Th2 cells to induce the AP-1 component. We propose that NF-ATp is a common regulatory factor for both Th1 and Th2 cytokine genes, and that the involvement of PKC-dependent factors, such as AP-1, may help determine Th1-/Th2-specific patterns of gene expression.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • CD3 Complex / immunology
  • Cell Line
  • Cloning, Molecular
  • Cyclosporine / metabolism
  • Cytokines / biosynthesis
  • Cytokines / genetics*
  • DNA
  • DNA-Binding Proteins / metabolism*
  • Female
  • Gene Expression Regulation*
  • Interleukin-2 / genetics
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / genetics
  • Ionomycin / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Promoter Regions, Genetic
  • T-Lymphocytes, Helper-Inducer / metabolism*
  • Transcription Factors / metabolism*
  • Transcriptional Activation

Substances

  • CD3 Complex
  • Cytokines
  • DNA-Binding Proteins
  • Interleukin-2
  • NFATC Transcription Factors
  • Nuclear Proteins
  • Transcription Factors
  • Interleukin-4
  • Ionomycin
  • Cyclosporine
  • DNA