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. 1979 Jan;76(1):457–461. doi: 10.1073/pnas.76.1.457

Impairment of cell-mediated immunity functions by dietary zinc deficiency in mice

Gabriel Fernandes 1, Madhavan Nair 1, Kazunori Onoe 1, Toshio Tanaka 1, Rachael Floyd 1, Robert A Good 1
PMCID: PMC382959  PMID: 311474

Abstract

Several immunologic features were analyzed in mice on a zinc-deficient diet [Zn(-)], in mice pair-fed a diet containing zinc [Zn(+)], in mice fed a Zn(+) diet ad lib, and in mice fed laboratory chow ad lib. When placed on a Zn(-) diet, 6- to 8-week-old A/Jax, C57BL/Ks, and CBA/H mice showed loss of body weight, low lymphoid tissue weight, and profound involution of the thymus within 4-8 weeks after initiation of the regimen. Approximately 50% of the mice on the Zn(-) diet developed severe acrodermatitis enteropathica (lesions on tail and paws) and diarrhea. Pair-fed mice on the Zn(+) diet did not show any of these symptoms. Mice on the Zn(-) diet showed the following immune deficiencies: (i) depressed plaque-forming cells against sheep erythrocytes after in vivo immunization; (ii) depressed T killer cell activity against EL-4 tumor cells after in vivo immunization; and (iii) low natural killer cell activity. However, antibody-dependent cell-mediated cytotoxicity against chicken erythrocytes was normal in the mice on the Zn(-) diet. Deficiency of T killer cell activity was not observed when immunization with EL-4 allogeneic lymphoma cells was carried out in vitro. Progressive loss of relative and absolute number of Thy 1.2+ cells and a proportionate relative increase in cells bearing Fc receptors was seen in spleen and lymph nodes of Zn(-) animals. It appears that zinc is an essential element for maintenance of normal T cell and other immune functions in vivo.

Keywords: thymic atrophy, T killer cells, natural killer cells

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Amos D. B., Bashir H., Boyle W., MacQueen M., Tiilikainen A. A simple micro cytotoxicity test. Transplantation. 1969 Mar;7(3):220–223. doi: 10.1097/00007890-196903000-00023. [DOI] [PubMed] [Google Scholar]
  2. Brummerstedt E., Flagstad T., Basse A., Andresen E. The effect of zinc on calves with hereditary thymus hypoplasia (lethal trait A 46). Acta Pathol Microbiol Scand A. 1971;79(6):686–687. doi: 10.1111/j.1699-0463.1971.tb01873.x. [DOI] [PubMed] [Google Scholar]
  3. Bullock W. W., Möller E. "Spontaneous" B cell activation due to loss of normal mouse serum suppressor. Eur J Immunol. 1972 Dec;2(6):514–517. doi: 10.1002/eji.1830020609. [DOI] [PubMed] [Google Scholar]
  4. Caggiano V., Schnitzler R., Strauss W., Baker R. K., Carter A. C., Josephson A. S., Wallach S. Zinc deficiency in a patient with retarded growth, hypogonadism, hypogammaglobulinemia and chronic infection. Am J Med Sci. 1969 May;257(5):305–319. doi: 10.1097/00000441-196905000-00003. [DOI] [PubMed] [Google Scholar]
  5. Chvapil M. New aspects in the biological role of zinc: a stabilizer of macromolecules and biological membranes. Life Sci. 1973 Oct 16;13(8):1041–1049. doi: 10.1016/0024-3205(73)90372-x. [DOI] [PubMed] [Google Scholar]
  6. Fernandes G., Halberg F., Yunis E. J., Good R. A. Circadian rhythmic plaque-forming cell response of spleens from mice immunized with SRBC. J Immunol. 1976 Sep;117(3):962–966. [PubMed] [Google Scholar]
  7. Fernandes G., Handwerger B. S., Yunis E. J., Brown D. M. Immune response in the mutant diabetic C57BL/Ks-dt+ mouse. Discrepancies between in vitro and in vivo immunological assays. J Clin Invest. 1978 Feb;61(2):243–250. doi: 10.1172/JCI108933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fernandes G., Yunis E. J., Good R. A. Age and genetic influence on immunity in NZB and autoimmune-resistant mice. Clin Immunol Immunopathol. 1976 Nov;6(3):318–333. doi: 10.1016/0090-1229(76)90085-4. [DOI] [PubMed] [Google Scholar]
  9. Fraker P. J., Haas S. M., Luecke R. W. Effect of zinc deficiency on the immune response of the young adult A/J mouse. J Nutr. 1977 Oct;107(10):1889–1895. doi: 10.1093/jn/107.10.1889. [DOI] [PubMed] [Google Scholar]
  10. Golden M. H., Harland P. S., Golden B. E., Jackson A. A. Zinc and immunocompetence in protein-energy malnutrition. Lancet. 1978 Jun 10;1(8076):1226–1228. doi: 10.1016/s0140-6736(78)92463-7. [DOI] [PubMed] [Google Scholar]
  11. Golden M. H., Jackson A. A., Golden B. E. Effect of zinc on thymus of recently malnourished children. Lancet. 1977 Nov 19;2(8047):1057–1059. doi: 10.1016/s0140-6736(77)91888-8. [DOI] [PubMed] [Google Scholar]
  12. Greaves M., Boyde T. R. Plasma-zinc concentrations in patients with psoriasis, other dermatoses, and venous leg ulceration. Lancet. 1967 Nov 11;2(7524):1019–1020. doi: 10.1016/s0140-6736(67)90290-5. [DOI] [PubMed] [Google Scholar]
  13. Gupta S., Fernandes G., Nair M., Good R. A. Spontaneous and antibody-dependent cell-mediated cytotoxicity by human T cell subpopulations. Proc Natl Acad Sci U S A. 1978 Oct;75(10):5137–5141. doi: 10.1073/pnas.75.10.5137. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Halsted J. A., Smith J. C., Jr Plasma-zinc in health and disease. Lancet. 1970 Feb 14;1(7642):322–324. doi: 10.1016/s0140-6736(70)90701-4. [DOI] [PubMed] [Google Scholar]
  15. Hambidge K. M., Hambidge C., Jacobs M., Baum J. D. Low levels of zinc in hair, anorexia, poor growth, and hypogeusia in children. Pediatr Res. 1972 Dec;6(12):868–874. doi: 10.1203/00006450-197212000-00003. [DOI] [PubMed] [Google Scholar]
  16. Handwerger B. S., Koren H. S. The nature of the effector cell in antibody-dependent, cell-mediated cytolysis (ADCC): the cytotoxic activity of murine tumor cells and peritoneal macrophages. Clin Immunol Immunopathol. 1976 Mar;5(2):272–281. doi: 10.1016/0090-1229(76)90032-5. [DOI] [PubMed] [Google Scholar]
  17. Henkin R. I. New aspects in the control of food intake and appetite. Ann N Y Acad Sci. 1977 Nov 30;300:321–334. doi: 10.1111/j.1749-6632.1977.tb19332.x. [DOI] [PubMed] [Google Scholar]
  18. Henkin R. I. Trace metals in endocrinology. Med Clin North Am. 1976 Jul;60(4):779–797. doi: 10.1016/s0025-7125(16)31861-2. [DOI] [PubMed] [Google Scholar]
  19. Hodes R. J., Handwerger B. S., Terry W. D. Synergy between subpopulations of mouse spleen cells in the in vitro generation of cell-mediated cytotoxicity: evidence for the involvement of a non-T cell. J Exp Med. 1974 Dec 1;140(6):1646–1659. doi: 10.1084/jem.140.6.1646. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Khalil M., Kabiel A., el-Khateeb S., Aref K., el-Lozy M., Jahin S., Nasr F. Plasma and red cell water and elements in protein-calorie malnutrition. Am J Clin Nutr. 1974 Mar;27(3):260–267. doi: 10.1093/ajcn/27.3.260. [DOI] [PubMed] [Google Scholar]
  21. Kiessling R., Haller O. Natural killer cells in the mouse: an alternative immune surveillance mechanism? Contemp Top Immunobiol. 1978;8:171–201. doi: 10.1007/978-1-4684-0922-2_6. [DOI] [PubMed] [Google Scholar]
  22. Krammer P. H., Hudson L., Sprent J. Fc-receptors, Ia-antigens, and immunoglobulin on normal and activated mouse T lymphocytes. J Exp Med. 1975 Dec 1;142(6):1403–1415. doi: 10.1084/jem.142.6.1403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. LEGG S. P., SEARS L. Zinc sulphate treatment of parakeratosis in cattle. Nature. 1960 Jun 25;186:1061–1062. doi: 10.1038/1861061a0. [DOI] [PubMed] [Google Scholar]
  24. Luecke R. W., Olman M. E., Baltzer B. V. Zinc deficiency in the rat: effect on serum and intestinal alkaline phosphatase activities. J Nutr. 1968 Mar;94(3):344–350. doi: 10.1093/jn/94.3.344. [DOI] [PubMed] [Google Scholar]
  25. Luecke R. W., Simonel C. E., Fraker P. J. The effect of restricted dietary intake on the antibody mediated response of the zinc deficient A/J mouse. J Nutr. 1978 May;108(5):881–887. doi: 10.1093/jn/108.5.881. [DOI] [PubMed] [Google Scholar]
  26. MacMahon R. A., Parker M. L., McKinnon M. C. Zinc treatment in malabsorption. Med J Aust. 1968 Aug 3;2(5):210–212. doi: 10.5694/j.1326-5377.1968.tb82733.x. [DOI] [PubMed] [Google Scholar]
  27. McConnell S. D., Henkin R. I. Altered preference for sodium chloride, anorexia, and changes in plasma and uninary zinc in rats fed a zinc-deficient diet. J Nutr. 1974 Sep;104(9):1108–1114. doi: 10.1093/jn/104.9.1108. [DOI] [PubMed] [Google Scholar]
  28. Miller J. F., Sprent J. Cell-to-cell interaction in the immune response. VI. Contribution of thymus-derived cells and antibody-forming cell precursors to immunological memory. J Exp Med. 1971 Jul 1;134(1):66–82. doi: 10.1084/jem.134.1.66. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Moynahan E. J. Letter: Acrodermatitis enteropathica: a lethal inherited human zinc-deficiency disorder. Lancet. 1974 Aug 17;2(7877):399–400. doi: 10.1016/s0140-6736(74)91772-3. [DOI] [PubMed] [Google Scholar]
  30. Moynahan E. J. Letter: Zinc deficiency and cellular immune deficiency in acrodermatitis enteropathica in man and zinc deficiency with thymic hypoplasia in fresian calves: a possible genetic link. Lancet. 1975 Oct 11;2(7937):710–710. doi: 10.1016/s0140-6736(75)90810-7. [DOI] [PubMed] [Google Scholar]
  31. Swenerton H., Hurley L. S. Severe zinc deficiency in male and female rats. J Nutr. 1968 May;95(1):8–18. doi: 10.1093/jn/95.1.8. [DOI] [PubMed] [Google Scholar]
  32. TUCKER H. F., SALMON W. D. Parakeratosis or zinc deficiency disease in the pig. Proc Soc Exp Biol Med. 1955 Apr;88(4):613–616. doi: 10.3181/00379727-88-21670. [DOI] [PubMed] [Google Scholar]
  33. West W. H., Cannon G. B., Kay H. D., Bonnard G. D., Herberman R. B. Natural cytotoxic reactivity of human lymphocytes against a myeloid cell line: characterization of effector cells. J Immunol. 1977 Jan;118(1):355–361. [PubMed] [Google Scholar]

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