ACTIVATION OF THE INTERLEUKIN-10 GENE IN THE HUMAN T-LYMPHOMA LINE HUT-78 - IDENTIFICATION AND CHARACTERIZATION OF NF-KAPPA-B BINDING-SITESIN THE REGULATORY REGION OF THE INTERLEUKIN-10 GENE

Interleukin-10 (IL-10) is a pleiotropic cytokine which has potent inhi bitory effects on macrophages and T cells, and contributes to the regu lation of proliferation and differentiation of B cells. Resting HuT 78 , a T-cell line derived from a Sezary lymphoma. produced significant a mounts of IL-10 compared with another T-cell Line, Jurkat. To elucidat e the mechanisms by which the IL-10 is expressed, we have analyzed the ir activity in human T-cell lines. We report here evidence that member s of the family of transcription factors nuclear factor-kappa B (NF-ka ppa B)/Rel can specifically recognize 3 identical sequences located in the 5'-regulatory region of IL-10 gene in resting HuT 78 cells, where as Jurkat cells expressed high levels of NF-kappa B consisting of p65 and p50 only upon activation with tumor necrosis factor-alpha (TNF-alp ha). In HuT 78 cells, p50 was the major component in the NF-kappa B co mplexes. Exogenous TNF-alpha and the monoclonal antibody to TNF-alpha did not affect IL-10 production and constitutive NF-kappa B binding le vels in HuT 78 cells. This study is the first demonstration of a role for NF-kappa B in the IL-10 gene expression, and suggests that its exp ression does not require TNF-alpha. These novel findings may account f or the specific IL-10 gene expression in T cells.