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The influence of zinc and citrate on T cell activation and differentiation in mixed lymphocyte cultures.

SCOPE: Zinc is important for a balanced immune system, but the mechanisms are not yet fully elucidated. One possibility is an interaction of zinc with the tricarbocylic acid cycle (TCA), in which zinc inhibits the mitochondrial aconitase leading to an increase in intracellular citrate concentration as described for prostate cells. Therefore, we studied the immune modulatory effects of zinc and citrate and their interaction in mixed lymphocyte cultures (MLC).

METHODS AND RESULTS: After allogeneic (MLC) or superantigen stimulation, the interferon-γ (IFNγ) production was quantified by ELISA and T cell subpopulations were determined by Western Blot. Intracellular concentrations of citrate and zinc were measured. Zinc and citrate reduce the IFNγ expression and the pro-inflammatory T helper cells (Th) 1 and Th17 in MLC. While zinc increases regulatory T cells, citrate reduces them. After superantigen stimulation IFNγ production is decreased only by citrate but increased by zinc. Zinc does not affect citrate concentration, while citrate impairs zinc uptake. Thus, zinc and citrate independently regulate IFNy expression.

CONCLUSION: These results may explain the immunosuppressive effect of blood products anticoagulated by citrate. In addition, high citrate consumption may lead to immunosuppressive effects, so upper limits for citrate should be established. This article is protected by copyright. All rights reserved.

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