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Copper Repletion Restores the Number and Function of CD4 Cells in Copper-Deficient Rats^1,2,

Shukal Bala^*,, and Mark L. Failla^*,,3

^* Vitamin and Mineral Nutrition Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, Agricultural Research Service, Beltsville, MD 20705-2350 Division for Evaluation of Anti-Viral Drug Products, Food and Drug Administration, Rockville, MD 20857 Department of Food, Nutrition and Food Service Management, The University of North Carolina at Greensboro, Greensboro, NC 27412-5001

Dietary copper deficiency decreases the number of splenic CD4 cells and mitogen-induced generation of interleukin-2 activity and DNA synthesis in cultures of splenic mononuclear cells. To determine the reversibility of these defects, Cu-deficient rats were fed a Cu-adequate diet for either 4, 7 or 11 d before preparation of cell cultures. Serum and hepatic concentrations of Cu attained 87 and 75%, respectively, of the control level after 4 d of dietary repletion. In contrast, interleukin-2 activity and [³H]thymidine incorporation in splenic cell cultures treated with T-cell mitogens were significantly greater than in cultures from Cu-deficient rats after 7, but not 4, d of dietary Cu repletion. The number of splenic CD4 cells was also greater after 7 d of dietary supplementation with Cu. Changes in the relative percentage and function of T-helper cells were highly correlated with one another and with hepatic Cu concentration. These observations indicate that an inadequate supply of dietary Cu reversibly suppresses the maturation and function of splenic T-helper cells.

KEY WORDS: • interleukin-2 • mitogenic reactivity • CD4 cells • copper deficiency • rats

¹ Presented in part at the 76th Annual Meeting of the Federation of American Societies for Experimental Biology, April 5–9, 1992, Anaheim, CA [Bala, S. & Failla, M. L. (1992) Kinetics of restoring function of splenic T-helper cells upon feeding copper to copper deficient rats. FASEB J. 6: A1209 (abs. 1532)].

² Supported in part by funds from the North Carolina Agriculture Research Project NC06287.

³ To whom correspondence should be addressed at: The University of North Carolina at Greensboro, FNS, A4 Park Bldg., Greensboro, NC 27412.

Manuscript received 31 August 1992. Revision accepted 11 January 1993.

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