HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-I TAX PROTEIN TRANS-ACTIVATES INTERLEUKIN-15 GENE-TRANSCRIPTION THROUGH AN NF-KAPPA-B SITE

Interleukin 15 (IL-15) mRNA is expressed in a wide variety of tissue t ypes. However, with the exception of some T cell lines, IL-15 transcri pt expression has not been described in T cells. Herein we demonstrate that IL-15 mRNA can be detected in freshly isolated normal T cells an d T cell lines. Furthermore, its expression is 3- to 4-fold higher in human T cell lymphotropic virus type I (HTLV-I)-infected T cells. By u sing reporter constructs bearing the 5' regulatory region of the IL-15 gene, we observed a positive correlation between HTLV-I Tax protein e xpression and IL-15 promoter activity in HTLV-I-infected T cells. Addi tionally, by using a Jurkat T cell transfectant that expresses Tax und er an inducible promoter, we demonstrated that the expression of IL-15 mRNA increased 3-fold as Tax was expressed, suggesting that the Tax p rotein activates IL-15 transcription. An NF-kappa B consensus sequence is located at the -75 and -65 region of the IL-15 5' regulatory regio n. Mutations in the NF-kappa B motif or deletion of this sequence abro gated the promoter activity in both HTLV-I-positive and Jurkat Tax-tra nsfectant cells. These data represent evidence for trans-activation of the IL-15 gene by the HTLV-I Tax protein through an NF-kappa B motif and suggest a potential role for IL-15 in HTLV-I-associated diseases s uch as adult T cell leukemia and HTLV-I-associated myopathy/tropical s pastic paraparesis.