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Control of in Vitro Lymphocyte Proliferation by Copper, Magnesium and Zinc Deficiency¹

Department of Molecular and Cellular Biology, Cleveland Clinic Foundation, Cleveland, OH 44106

Plant lectin-induced proliferation of lymphocytes in vitro in both whole-spleen cell and T cell-enriched cultures was markedly effected by depletion of media copper, magnesium or zinc. The T lymphocyte-oriented mitogens concanavalin A and phytohemagglutinin and the B lymphocyte-oriented mitogen lipopolysaccharide were used to study variations in [³H]thymidine incorporation in lymphocytes cultured in media deficient in one mineral element. Since the stimulatory action of these mitogens also relates to the interaction of lymphocytes with accessory cells, we looked at the phagocytic ability of accessory cells cultured in the depleted media. In addition, we determined the variations in cell surface markers for B lymphocytes (Ia), T lymphocytes (Thy 1.2, Lyt 1 and Lyt 2) and accessory cells (Ia). Media depleted of copper, magnesium or zinc did not support normal T-lymphocyte proliferation but did support normal B-lymphocyte proliferation. The phagocytic ability of magnesium-deficient and zinc-deficient accessory cells was also depressed. This was related to depressed Ia expressions in the magnesium-deficient and zinc-deficient whole-spleen cell cultures. Total T-lymphocyte numbers, as well as Lyt 1⁺ cell percentages, were unchanged by media depletion, whereas Lyt 2⁺ cell percentages were depressed in both copper-deficient and magnesium-deficient splenocyte cultures.

KEY WORDS: • lymphocytes • accessory cells • proliferation • copper • magnesium • zinc

¹ Supported in part by a grant from the U.S. Public Health Service of the National Institutes of Health: CA 34107 from the National Cancer Institute.

Manuscript received 6 January 1984.