Skip to main content
Log in

Supplementation with selenium augments the functions of natural killer and lymphokine-activated killer cells

  • Original Articles
  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

This study examined the effects of dietary (2.0 ppm for 8 wk) and in vitro (1×10−7 M) supplementation with selenium (Se, as sodium selenite) on the activity of spleen natural killer (NK) cells and plastic-adherent lymphokine-activated killer (A-LAK) cells from C57B1/6J male mice. Dietary supplementation with Se resulted in a significant increase in the lytic activity of activated NK cells, and cells from these highly lytic effector cell populations expressed significantly higher numbers of intermediate affinity interleukin-2 receptors (II-2R)/cell. In the presence of high concentrations of II-2 and 1×10−7 M Se, resting populations of spleen NK cells developed into A-LAK cells that had a significantly enhanced ability to proliferate, as indicated by the significantly higher amounts of nuclear3H-thymidine incorporation, and a significantly augmented cytolytic activity against both NK-sensitive and NK-resistant target cells. Se appears to enhance the lytic activity of activated NK cells and to augment the proliferation, expansion, and lytic activity of A-LAK cells in the presence of high concentrations of Il-2 through its ability to enhance the expression of intermediate affinity Il-2R on these cells.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. R. B. Herberman, C. W. Reynolds, and J. R. Ortaldo, Mechanism of cytotoxicity by natural killer cells,Annu. Rev. Immunol. 4, 651–680 (1985).

    Article  Google Scholar 

  2. G. Trinchierl, Biology of natural killer cells,Adv. Immunol. 47, 187–376 (1989).

    Google Scholar 

  3. N. L. Vujanovic, R. B. Herberman, A. A. Maghazachi, and J. C. Hiserodt, Lymphokine activated killer cells in rats. III. A simple method for the purification of large granular lymphocytes and their rapid expansion and conversion into lymphokine-activated killer cells,J. Exp. Med. 167, 15–29 (1988).

    Article  PubMed  CAS  Google Scholar 

  4. W. J. Leonard and J. P. Siegel, The interleukin-2 receptor complex and its role in the induction of nonspecific cytotoxicity, inInterleukin-2 and Killer Cells in Cancer, E. Lotzova and R. B. Herberman, eds., CRC, Boca Raton, FL, pp. 305–317 (1990).

    Google Scholar 

  5. M. A. Beilstein, P. D. Whanger, and I. Wong, Selenium requirement and metabolism by mammalian cells in vitro, inSelenium in Biology and Medicine, Part A, G. F. Combs, J. E. Spallholz, O. H. Levander, and J. E. Oldfield, eds., Van Nostrand Reinhold, New York, pp. 197–212 (1987).

    Google Scholar 

  6. L. Kiremidjian-Schumacher and G. Stotzky, Selenium and immune responses. A review,Environ. Res. 42, 277–303 (1987).

    Article  PubMed  CAS  Google Scholar 

  7. L. Kiremidjian-Schumacher, M. Roy, H. I. Wishe, M. W. Cohen, and G. Stotzky, Selenium and immune cell functions: I. Effect on lymphocyte proliferation and production of interleukin-1 and interleukin-2,Proc. Soc. Exp. Biol. Med. 193, 136–142 (1990).

    PubMed  CAS  Google Scholar 

  8. M. Roy, L. Kiremidjian-Schumacher, H. I. Wishe, M. W. Cohen, and G. Stotzky, Selenium and immune cell functions: II. Effect on lymphocyte-mediated cytotoxicity,Proc. Soc. Exp. Biol. Med. 193, 143–148 (1990).

    PubMed  CAS  Google Scholar 

  9. M. Roy, L. Kiremidjian-Schumacher, H. I. Wishe, M. W. Cohen, and G. Stotzky, Supplementation with selenium and human immune cell functions. I. Effect on lymphocyte proliferation and interleukin 2 receptor expression,Biol. Trace Elem. Res. 41, 103–114 (1994).

    Article  PubMed  CAS  Google Scholar 

  10. L. Kiremidjian-Schumacher, M. Roy, H. I. Wishe, M. W. Cohen, and G. Stotzky, Supplementation with selenium and human immune cell functions. II. Effect on cytotoxic lymphocytes and natural killer cells,Biol. Trace Elem. Res. 41, 115–127 (1994).

    PubMed  CAS  Google Scholar 

  11. M. Roy, L. Kiremidjian-Schumacher, H. I. Wishe, M. W. Cohen, and G. Stotzky, Effect of selenium on the expression of high affinity interleukin 2 receptors,Proc. Soc. Exp. Biol. Med. 200, 36–43 (1992).

    PubMed  CAS  Google Scholar 

  12. M. Roy, L. Kiremidjian-Schumacher, H. I. Wishe, M. W. Cohen, and G. Stotzky, Selenium supplementation enhances the expression of interleukin 2 receptor subunits and internalization of interleukin 2,Proc. Soc. Exp. Biol. Med. 202, 295–301 (1993).

    PubMed  CAS  Google Scholar 

  13. J. E. Spallholz, G. F. Collins, and K. A. Schwartz, A single-test-tube method for the fluorometric determination of selenium,Bioinog. Chem. 9, 453–459 (1978).

    Article  CAS  Google Scholar 

  14. M. H. Julius, E. Simpson, and L. A. Herzenberg, A rapid method for the isolation of functional thymus derived murine lymphocytes,Eur. J. Immunol. 3, 645–649 (1973).

    Article  PubMed  CAS  Google Scholar 

  15. M. G. Roncarolo, M. Bigler, J. B. Haanen, H. Yssel, R. Bacchetta, J. E. de Vries, and H. Spits, Natural killer cell clones can effectively process and present protein antigens,J. Immunol. 147, 781–787 (1991).

    PubMed  CAS  Google Scholar 

  16. Y. Gunji, N. L. Vujanovic, J. C. Hiserodt, R. B. Herberman, and E. Gorelik, Generation and characterization of putified adherent lymphokine-activated killer cells in mice,J. Immunol. 142, 1748–1754 (1989).

    PubMed  CAS  Google Scholar 

  17. P. D. Brown and F. V. Sepulveda, A rabbit jejunal isolated enterocyte preparation suitable for transport studies,J. Physiol. 363, 257–270 (1985).

    PubMed  CAS  Google Scholar 

  18. L. D. Koller, J. H. Exson, P. A. Talcott, C. A. Osborne, and G. M. Henningsen, Immune responses in rats supplemented with selenium,Clin. Exp. Immunol. 63, 570–576 (1986).

    PubMed  CAS  Google Scholar 

  19. C. A. Biron, H. A. Young, and M. T. Kasaian, Interleukin 2-induced proliferation of murine natural killer cells in vivo,J. Exp. Med. 71, 173–188 (1990).

    Article  Google Scholar 

  20. M. J. Robertson and J. Ritz, Role of IL-2 receptors in NK cell activation and proliferation, inNK Cell Mediated Cytotoxicity: Receptors, Signaling, and Mechanisms. E. Lotzova and R. Herberman, eds., CRC, Boca Raton, FL, pp. 183–206 (1992).

    Google Scholar 

  21. M. J. Robertson, M. A. Caligiuri, T. J. Manley, H. Levine, and J. Ritz, Human natural killer cell adhesion molecules Differential expression after activation and participation in cytolysis.J. Immunol. 145, 3194–3201 (1990).

    PubMed  CAS  Google Scholar 

  22. T. Timonen, C. G. Gahmberg, and M. Patarroyo, Participation of CD11a-c/CD18, CD2, and RGD-binding receptors in endogenous and interleukin 2-stimulated NK activity of CD3-negative large granular lymphocytes,Int. J. Cancer 46, 1035–1040 (1990).

    Article  PubMed  CAS  Google Scholar 

  23. J. D. Bonnema, K. A. Rivlin, A. T. Ting, R. A. Schoon, R. T. Abraham, and P. J. Leibson, Cytokine-enhanced NK cell-mediated cytotoxicity. Positive modilatory effect of Il-2 and Il-12 on stimulus-dependent granule exocytosis,J. Immunol. 152, 2098–2103 (1994).

    PubMed  CAS  Google Scholar 

  24. K. A. Smith and D. A. Cantrell, Interleukin-2 regulates its own receptors,Proc. Natl. Acad. Sci. USA 82, 864–868 (1985).

    Article  PubMed  CAS  Google Scholar 

  25. K. A. Smith, Interleukin-2: Inception, impact, and implications,Science 240, 1169–1176 (1988).

    Article  PubMed  CAS  Google Scholar 

  26. P. V. Nash and A. M. Mastro, Activation of primary lymphocytes requires prolonged lectin stimulation,J. Leuk. Biol. 53, 73–78 (1993).

    CAS  Google Scholar 

  27. N. S. Gutgsell and T. R. Malek, Formation of high affinity IL-2 receptors is dependent on a nonligand binding region of the α subunit,J. Immunol. 153, 3899–3907 (1994).

    PubMed  CAS  Google Scholar 

  28. Y. Minami, T. Kono, T. Miyazaki, and Taniguchi, The Il-2 receptor complex: Its structure, function, and target genes,Annu. Rev. Immunol. 11, 245–267 (1993).

    Article  PubMed  CAS  Google Scholar 

  29. M. A. Caligiuri, A. Zmuidzinas, T. J. Manley, H. Levine, K. A. Smith, and J. Ritz, Functional consequences of interleukin 2 receptor expression on resting human lymphocytes. Identification of a novel natural killer cell subset with high affinity receptors.J. Exp. Med. 171, 1509–1526 (1990).

    Article  PubMed  CAS  Google Scholar 

  30. D. Vitolo, N. L. Vujanovic, H. Rabinowich, M. Schlesinger, R. B. Herberman, and T. L. Whiteside, Rapid Il-2-induced adherence of human natural killer cells. Expression of mRNA for cytokines and IL-2 receptors in adherent NK cells,J. Immunol. 151, 1926–1937 (1993).

    PubMed  CAS  Google Scholar 

  31. W. H. Chambers, A. B. DeLeo, N. L. Vujanovic, and J. C. Hiserodt, Role of the interleukin-2 receptor in the growth and regulation of LAK activity, inInterleukin-2 and Killer Cells in Cancer, E. Lotzova and R. B. Herberman, eds. CRC, Boca Raton, FL, pp. 339–361 (1990).

    Google Scholar 

  32. O. de la Calle-Martin, J. Alberola-Ila, P. Engel, J. L. Ingles, V. Fabregat, J. J. Barcelo, F. Lozano, and T. Gallard, Impaired post-transcriptional expression of interleukin-2 receptor in pokeweed mitogen-activated T cells,Eur. J. Immunol. 22, 897–902 (1992).

    Article  PubMed  Google Scholar 

  33. A. D. Weinberg and S. L. Swain, IL-2 receptor (TAC antigen) protein expression is down-regulated by the 5′-untranslated region of the mRNA,J. Immunol. 144, 4712–4720 (1990).

    PubMed  CAS  Google Scholar 

  34. T. C. Stadtman, Selenium biochemistry,Annu. Rev. Biochem. 59, 111–127 (1990).

    Article  PubMed  CAS  Google Scholar 

  35. M. J. Berry, L. Banu, and R. Laresen, Type I iodothyronine deiodinase is a selenocysteine-containing enzyme,Nature 349, 438–440 (1991).

    Article  PubMed  CAS  Google Scholar 

  36. M. J. Christensen and K. W. Burgener, Dietary selenium stabilizes glutathione peroxidase mRNA in rat liver,Am. Inst. Nutr. 122, 1620–1626 (1992).

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kiremidjian-Schumacher, L., Roy, M., Wishe, H.I. et al. Supplementation with selenium augments the functions of natural killer and lymphokine-activated killer cells. Biol Trace Elem Res 52, 227–239 (1996). https://doi.org/10.1007/BF02789164

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02789164

Index Entries

Navigation