Positive and negative regulation of IL-2 gene expression: Role of multiple regulatory sites

Liqian Zhang, Gary J. Nabel

Research output: Contribution to journalArticlepeer-review

Abstract

Interleukin 2 (IL-2) is an important lymphokine required in the process of T cell activation, proliferation, clonal expansion and differentiation. The IL-2 gene displays both T cell specific and inducible expression: it is only expressed in CD4+ T cells after antigenic or mitogenic stimulation. Several cis-acting regulatory sites are required for induction of the IL-2 gene after stimulation. In this study, we have analysed the function of these cis-acting regulatory sites in the context of the native IL-2 enhancer and promoter sequence. The results of this study suggest that the NFAT (-276 to -261), the distal octamer (-256 to -248) and the proximal octamer (-75 to -66) sites not only act as enhancers of IL-2 gene transcription in the presence of cellular stimulation, but also have a silencing effect on IL-2 gene expression in resting cells. Two other sites display disparate effects on IL-2 gene expression in different T leukemia cell lines: the distal purine box (-291 to -277) and the proximal purine box sites (-145 to -128). Finally, the AP-1 (-186 to -176) and the κB sites (-206 to -195) respond to different cellular activation in EL4 cells. The AP-1 site mediated the response to PMA stimulation while the κB site responded to IL-1 stimulation. These data suggest that the regulation of IL-2 gene expression is a complex process and multiple cis-acting regulatory sites interact to exert different effects in T cells representative of alternative stages of differentiation.

Original languageEnglish (US)
Pages (from-to)221-228
Number of pages8
JournalCytokine
Volume6
Issue number3
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • Gene regulation
  • Interleukin 2
  • T cell activation

ASJC Scopus subject areas

  • Endocrinology
  • Molecular Biology
  • Immunology
  • Immunology and Allergy

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