Human T cell leukemia virus type I Tax enhances IL‐4 gene expression in T cells

• Published in: European journal of immunology 2001-09, Vol.31 (9), p.2623-2632
• Main Authors: Li‐Weber, Min, Giaisi, Marco, Chlichlia, Katerina, Khazaie, Khashayarsha, Krammer, Peter H.
• Format: Article
• Language: English
• Subjects: CCAAT-Enhancer-Binding Protein-beta - metabolism; CCAAT‐enhancer binding protein; Cells, Cultured; Gene Products, tax - genetics; Gene Products, tax - pharmacology; HTLV‐1; Human T-lymphotropic virus 1; Humans; IL‐4; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Jurkat Cells; NF-IL6 protein; Promoter Regions, Genetic; Response Elements; RNA, Messenger - biosynthesis; T-Lymphocytes - immunology; Tax; Tax protein; Transcriptional Activation; Transfection
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/1521-4141(200109)31:9<2623::AID-IMMU2623>3.0.CO;2-4

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, enhancesPRE‐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.