Increase of Intracellular Zinc Levels Rather Than Zinc Influx Inhibits Interleukin-2 Production in Zinc Supplemented Jurkat Cells

The essential trace element zinc is a well-known modulator of T cell activation. There have been contradictory findings for the impact of zinc supplementation on T cell activation. In our study, we aimed to analyze IL-2 production in Jurkat T cells during zinc supplementation in response to different stimuli. We found that zinc strongly suppresses IL-2 production in Jurkat cells stimulated with phorbol 12-myristate 13-acetate (PMA)/calcimycin or phytohemagglutinin (PHA)/calcimycin. In contrast, zinc had no impact on IL-2 production after PHA stimulation alone, suggesting the inhibitory zinc-effect was linked to high calcium influx. To distinguish if the observed IL-2 suppression is due to either potential competing effects of zinc influx or simple elevation of intracellular zinc levels, we pretreated the Jurkat cells with the zinc ionophore pyrithione for an increase of intracellular zinc before the stimulation. It was sufficient to suppress IL-2 expression even when the cells were not further supplemented with zinc during stimulation. We propose that zinc's inhibitory effects on phosphatases stabilize the phosphorylated NFAT and thus block IL-2 expression. Our findings underline the importance of a balanced zinc status for proper immune functions and suggest a supporting effect of zinc during immunosuppressive treatments.