Human T cell leukemia virus type I tax enhances IL-4 gene expression in T cells

Min Li-Weber, Marco Giaisi, Katerina Chlichlia, Khashayarsha Khazaie, Peter H. Krammer

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

The human T cell leukemia virus type-1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL). Since the HTLV-I-encoded transactivator Tax has been shown to activate many cellular genes including cytokine genes interleukin (IL-)1α, 2, 5, 6, 8, 10 and 15, we ask whether Tax also affects IL-4 expression. In this study, we show that addition of recombinant Tax proteins greatly enhances IL-4 secretion in human peripheral primary T cells. Transient transfection studies showed that ectopic expression of Tax significantly enhanced IL-4 promoter activity. The IL-4 promoter contains a strong NF-IL6 (PRE-I element) and a NF-AT/NF-κB overlapping site (P1 element). We show that expression of Tax stimulates NF-IL6 binding to the PRE-I element and, consequently, enhances PRE-I-mediated transcriptional activity. Using Jurkat T cell lines which stably express Tax fused to the hormone binding domain of the human estrogen receptor (ER), we show that Tax enhances endogenous IL-4 mRNA expression and increases IL-4 promoter activity in a hormone-dependent manner. Mutation analysis revealed that the IL-4 PRE-I (NF-IL6 site) and the P1 (NF-AT/NF-κB site) are involved in Tax-mediated transactivation. Our studies provide the first evidence of the functional involvement of Tax in IL-4 gene regulation.

Original languageEnglish (US)
Pages (from-to)2623-2632
Number of pages10
JournalEuropean Journal of Immunology
Volume31
Issue number9
DOIs
StatePublished - Oct 8 2001

Keywords

  • CCAAT-enhancer binding protein
  • HTLV-1
  • IL-4
  • Tax

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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