Octamer proteins inhibit IL-4 gene transcription in normal human CD4 T cells

R. Q. Cron, B. Zhou, M. W. Brunvand, D. B. Lewis

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The balance of Th1 (eg, interleukin-2 (IL-2)) and Th2 (eg, IL-4) cytokines produced by CD4 T cells markedly influences the outcome of the adaptive immune response. Although octamer transcription factor proteins increase IL-2 transcription in T cells, their role in IL-4 gene transcription remains controversial. We have previously shown and now confirm that the proximal octamer binding site of the human IL-4 promoter, which separates the two most proximal NFAT binding sites, is bound prior to, but not after, activation in vivo. Since these two NFAT sites are essential for optimal IL-4 promoter activity, this suggested that prior engagement by octamer proteins might prevent adjacent NFAT binding and inhibit IL-4 gene transcription. In support of this hypothesis, here we show that NFAT proteins are unable to bind to a combined octamer/NFAT site unless the octamer proteins are competed away. Moreover, activity of an IL-4 reporter gene mutated in the proximal octamer binding site is increased compared to the wild-type promoter in human peripheral blood CD4 T cells. In addition, over-expression of either Oct-1 or Oct-2 decreased wild-type IL-4 promoter activity, while increasing IL-2 promoter activity. No decrease in promoter activity was seen when Oct-1 or Oct-2 was over-expressed with the octamer-mutant IL-4 reporter gene. Thus, octamer proteins are candidates to promote a Th1 rather than Th2 pattern of cytokine gene expression by activated CD4 T cells.

Original languageEnglish (US)
Pages (from-to)464-468
Number of pages5
JournalGenes and Immunity
Volume2
Issue number8
DOIs
StatePublished - Dec 2001
Externally publishedYes

Keywords

  • Human
  • IL-4
  • Interleukin-2
  • Octamer
  • T cell
  • Transcription

ASJC Scopus subject areas

  • Immunology
  • Genetics
  • Genetics(clinical)

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