Copper deficiency reversibly impairs DNA synthesis in activated T lymphocytes by limiting interleukin 2 activity.
The essentiality of adequate copper (Cu) nutriture for normal T-cell function in laboratory and domestic animals is well established. However, specific biochemical roles of Cu in the maturation and activation of T cells have not been defined. Previous work showed that when cultures of splenic mononuclear cells (MNCs) from Cu-deficient rats were exposed to T-cell mitogens, DNA synthesis was markedly reduced despite normal up-regulation of interleukin 2 (IL-2) receptors, transferrin receptors, and class II major histocompatibility complex molecules. In the present study, IL-2 activity in PHA-treated cultures of MNCs from Cu-deficient rats was 40-50% that of controls as determined by bioassay. Addition of rat IL-2 to phytohemagglutinin-treated cultures of MNCs from Cu-deficient rats increased blastogenic activity to control levels, demonstrating that Cu deficiency does not inhibit transition of quiescent cells to the competence phase of the activation process. Moreover, supplementation of MNC cultures from Cu-deficient rats with physiological levels of Cu enhanced IL-2 activity and DNA synthesis in response to phytohemagglutinin. These data indicate that IL-2 activity in cultures of activated splenic T lymphocytes from Cu-deficient rats is insufficient for optimal blastogenesis.
Bala
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Vitamin and Mineral Nutrition Laboratory, Beltsville Human Nutrition Research Center, U.S. Department of Agriculture, MD 20705-2350.
Failla
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D000818:Animals; D002478:Cells, Cultured; D003300:Copper / Q000172:deficiency* / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D007700:Kinetics; D008213:Lymphocyte Activation; D008297:Male; D008345:Manganese / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium; D015032:Zinc / Q000494:pharmacology
D007376:Interleukin-2; D014316:Tritium; D008345:Manganese; D003300:Copper; D015032:Zinc; D013936:Thymidine