The human T cell leukemia virus type-1 (HTLV-1) is the etiologic agent of a
dult T cell leukemia (ATL). Since the HTLV-I-encoded transactivator Tax has
been shown to activate many cellular genes including cytokine genes interl
eukin (IL-)1 alpha, 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 pr
oteins greatly enhances IL-4 secretion in human peripheral primary T cells.
Transient transfection studies showed that ectopic expression of Tax signi
ficantly enhanced IL-4 promoter activity. The IL-4 promoter contains a stro
ng NF-IL6 (PRE-I element) and a NF-AT/NF-kappaB overlapping site (P1 elemen
t). We show that expression of Tax stimulates NF-IL6 binding to the PRE-I e
lement and, consequently, enhances PRE-I-mediated transcriptional activity.
Using Jurkat T cell lines which stably express Tax fused to the hormone bi
nding 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 (N
F-IL6 site) and the P1 (NF-AT/NF-kappaB site) are involved in Tax-mediated
transactivation. Our studies provide the first evidence of the functional i
nvolvement of Tax in IL-4 gene regulation.