Activation of the interleukin‐10 gene in the human T lymphoma line HuT 78: identification and characterization of NF‐κ B binding sites in the regulatory region of the interleukin‐10 gene

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Abstract
Interleukin‐10 (IL‐10) is a pleiotropic cytokine which has potent inhibitory effects on macrophages and T cells, and contributes to the regulation of proliferation and differentiation of B cells. Resting HuT 78, a T‐cell line derived from a Sezary lymphoma, produced significant amounts of IL‐10 compared with another T‐cell line, Jurkat. To elucidate the mechanisms by which the IL‐10 is expressed, we have analyzed their activity in human T‐cell lines. We report here evidence that members of the family of transcription factors nuclear factor‐κ B (NF‐κ B)/Rel can specifically recognize 3 identical sequences located in the 5′‐regulatory region of IL‐10 gene in resting HuT 78 cells, whereas Jurkat cells expressed high levels of NF‐κ B consisting of p65 and p50 only upon activation with tumor necrosis factor‐α (TNF‐α). In HuT 78 cells, p50 was the major component in the NF‐κ B complexes. Exogenous TNF‐α and the monoclonal antibody to TNF‐α did not affect IL‐10 production and constitutive NF‐κ B binding levels in HuT 78 cells. This study is the first demonstration of a role for NF‐κ B in the IL‐10 gene expression, and suggests that its expression does not require TNF‐α. These novel findings may account for the specific IL‐10 gene expression in T cells.