The -180 site of the IL-2 promoter is the target of CREB/CREM binding in T cell anergy

Jonathan D. Powell, Cara G. Lerner, Gerald R. Ewoldt, Ronald H. Schwartz

Research output: Contribution to journalArticlepeer-review

Abstract

Anergic T cells display a marked decrease in their ability to produce IL-2 even in the presence of optimal TCR and costimulatory signals. Using IL- 2 enhancer/promoter-driven reporter constructs, we have previously identified a region that appears to be a target for cis transcriptional repression in anergy. This region of the promoter, which shares partial homology with a consensus AP-1-binding sequence, is located about -180 bp from the transcriptional start site. In the present study, we demonstrate that cAMP response element-binding protein/cAMP response element modulator (CREB/CREM), activating transcription factor-2/c-Jun, and Jun-Jun/Oct complexes bind to this site. However, the induction of anergy by prolonged stimulation through the TCR led to an increase in binding of only the CREB/CREM complex. Furthermore, the level of binding of this complex appeared to be up-regulated in both resting and restimulated anergic T cells. Finally, an IL-2 promoter- driven reporter construct that contained a mutation that specifically reduced the binding of the CREB/CREM complex displayed a decreased ability to be affected by anergy, while a construct that contained a mutation that decreased the binding of the Jun-Jun/Oct complex was still susceptible to anergy. These findings suggest that the - 180 region of the IL-2 promoter is the target of a CREB/CREM transcriptional inhibitor that contributes to the repression of IL-2 production in T cell anergy.

Original languageEnglish (US)
Pages (from-to)6631-6639
Number of pages9
JournalJournal of Immunology
Volume163
Issue number12
StatePublished - Dec 28 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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