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Article

Transcriptional Regulation of Interleukin-2 Gene Expression Is Impaired by Copper Deficiency in Jurkat Human T Lymphocytes

University of North Carolina at Greensboro, Dept. of Nutrition and Foodservice Management, Greensboro, NC 27402

Copper deficiency reduces secretion of the cytokine interleukin-2 (IL-2) by activated rodent splenocytes, human peripheral blood mononuclear cells and Jurkat cells, a human T lymphocyte cell line. Previous studies showed that low Cu status also decreased the level of IL-2 mRNA in activated Jurkat cells by 50%. Synthesis of this cytokine is regulated by alterations in transcription of the IL-2 gene and the stability of IL-2 mRNA. To determine if Cu status influenced promoter activity of the IL-2 gene, Jurkat cells were transfected with a luciferase reporter gene construct containing the entire 300 bp human IL-2 promoter/enhancer sequence. Cu deficiency was induced by incubating stably transfected cells with the Cu chelator 2,3,2-tetraamine for 35 h prior to activating cells with phytohemagglutinin-P and phorbol myristate acetate. Luciferase activity in lysates of Cu-deficient cells was approximately 50% lower in several multiclonal and clonal cell lines of stably transfected cells than in replicate cultures that were not exposed to chelator. The relative levels of endogenous IL-2 bioactivity and luciferase activity were highly correlated in the transfected cell lines. The chelator-mediated reduction in reporter gene activity was dose-dependent at levels of 5–40 µmol 2,3,2-tetraamine/L. The addition of a slight molar excess of Cu, but not Zn or Fe, to medium containing 2,3,2-tetraamine prevented the decline in luciferase activity. IL-2 mRNA stability in parental Jurkat cells was independent of Cu status. These data indicate that decreased cellular Cu attenuates IL-2 synthesis in T lymphocytes by inhibiting transcription of the IL-2 gene.

KEY WORDS: • Copper • human T cell • interleukin-2 • gene expression • transcriptional regulation

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