Skip to main content
SpringerLink
Log in
Book cover

Mechanisms of Lymphocyte Activation and Immune Regulation pp 275–283Cite as

Activation of Natural Killer (NK) Cells and Mechanism of Their Cytotoxic Effects

  • Chapter

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 213))

Abstract

Natural killer (NK) cells are lymphoid cells with spontaneous activity against a wide variety of tumor cell lines and against primary or metastatic tumor cells (1–3). It is now possible to isolate highly enriched populations of NK cells and demonstrate that this cytotoxic activity is mediated predominantly, if not solely, by a small subpopulation of lymphocytes, morphologically identified as large granular lymphocytes (LGL). In addition, a large proportion of LGL have NK activity (3,4). NK activity has been found to be positively regulated by a variety of agents, with the interferons and interleukin 2 (IL-2) being identified as the principal cytokines mediating this stimulation of reactivity (5).

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. R. B. Herberman, and J. R. Ortaldo. Natural Killer cells: Their role in defenses against disease. Science 214:24, (1981).

    Article  ADS  Google Scholar 

  2. J. R. Ortaldo, and R. B. Herberman. Heterogeneity of natural killer cells. Annu. Ref. Immunol. 2:359. (1984).

    Article  Google Scholar 

  3. R. B. Herberman. Multiple functions of natural killer cells, including immunoregulation as well as resistance to tumor growth. Concepts Immunopathol. 1:96, (1985).

    Google Scholar 

  4. T. Timonen, J. R. Ortaldo, and R. B. Herberman. Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J. Exp. Med. 153:569, (1981).

    Article  Google Scholar 

  5. R. B. Herberman, and A. Santoin. Regulation of natural killer (NK) cell activity. In Mihich, E. (Ed.): Biological Responses in Cancer, Vol. 2. New York, Pleunum Pub. Corp. New York, Plenum Publ. Corp. pp. 121–144, (1984).

    Google Scholar 

  6. T. Timonen, J. R. Ortaldo, B. M. Stadler, G. D. Bonnard, S. O. Sharrow, and R. B. Herberman. Cultures of purified human natural killer cells: Growth in the presence of interleukin 2. Cell Immunol. 72:178, (1982).

    Article  Google Scholar 

  7. S. Yamada, F. W. Ruscetti, W. R. Overton, R. B. Herberman, and J. R. Ortaldo. Regulation of human large granular lymphocytes and T cell growth and function by recombinant interleukin 2. I. Induction of interleukin 2 receptor and promotion of growth of cells with enhance cytotoxicity. Manuscript submitted.

    Google Scholar 

  8. G. D. Bonnard, K. Yasaka, and D. Jacobson. Ligand-activated mitogenic factor-induced T-cell proliferation. Adsorption of mitogenic factor by activated T cells. J. Immunol. 123:2704–2708, (1979).

    Google Scholar 

  9. J. E. Talmadge, R. H. Wiltrout, D. F. Counts, R. B. Herberman, T. McDonald, and J. Ortaldo. Proliferation of human peripheral blood lymphocytes induced by recombinant human interleukin-2: Contribution of large granular lymphocytes and T lymphocytes. Manuscript submitted to Cell Immunology.

    Google Scholar 

  10. K. Itoh, A. B. Tilden, K. Kumagai, and C. M. Balch. Leu 11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (IL-2) included activated kill (AK) cells. J. Immunol. 134:802–807, (1985).

    Google Scholar 

  11. E. A. Grimm, R. J. Robb, J. A. Roth, L. M. Neckers, L. B. Lachman, D. J. Wilson, and S. A. Rosenberg. Lymphokine-activated killer cell phenomenon III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine activated killer cells. J. Exp. Med. 158:1356, (1983).

    Article  Google Scholar 

  12. J. E. Ortaldo, A. T. Mason, J. P. Gerard, L. E. Henderson, W. Farrar, R. F. Hopkins III, R. B. Herberman, and H. Rabin. Effects of natural and recombinant IL-2 on regulation of IFN production and natural killer activity: Lack of involvement of the Tac antigen for these immunoregulatory effects. J. Immunol. 133:779, (1984).

    Google Scholar 

  13. R. B. Herberman. NK Cells and Other Natural Effector Cells. New York: Academic (1982).

    Google Scholar 

  14. R. B. Herberman, Calleweart, eds. Mechanisms of Cytotoxicity by NK Cells. Orlando, Fla: Academic (1985).

    Google Scholar 

  15. S. Targan, R. L. Deem, in R. B. Herberman and D. Calleweart, (eds). Mechanisms of Cytotoxicity by NK Cells. Orlando, Academic Press, Inc., p 155, (1985).

    Google Scholar 

  16. B. Perussia, O. Acuto, C. Terhorst, J. Faust, R. Lazaruz, V. Fanning, and G. Trinchieri. Human natural killer cells analyzed by B731.1, a monoclonal antibody blocking Fc receptor functions. J. Immunol. 130:2142, (1983).

    Google Scholar 

  17. C. W. Reynolds, S. O. Sharrow, J. R. Ortaldo, and R. B. Herberman. Natural killer (NK) activity in the rat. II. Analysis of surface antigens on LGL by flow cytometry. J. Immunol. 127:2204. (1981).

    Google Scholar 

  18. J. R. Ortaldo, S. O. Sharrow, T. Timonen, and R. B. Herberman. Determination of surface antigens on highly purified human NK cells by flow cytometry with monoclonal antibodies. J. Immunol. 127:2401. (1981).

    Google Scholar 

  19. R. Kiessling, E. Klein, H. Pross, and H. Wigzell. “Natural” killer cells in the mouse. II. Cutoptoxic cells with specificity for mouse Maloney leukemia cells. Characteristics of the killer cells. Eur. J. Immunol. 5:117, (1975).

    Article  Google Scholar 

  20. J. C. Hiserodt, K. A. Laybourn and J. Varani. Expression of a laminin-like substance on the surface of murine natural killer (NK) lymphocytes and its role in NK recognition of tumor target cells. J. Immunol. 135:1484, (1985).

    Google Scholar 

  21. Y. Yanagi, N. Caccia, M. Kronenberg, B. Chin, J. Ropder, D. Rohel, T. Kiyohara, R. Lauzon, B. Toyanaga, O. K. Rosenthal, G. Dennert, H. Acha-Orbea, H. Hengartner, L. Hood, and T. W. Mak. Gene rearrangement in cells with natural killer activity and expression of the -chain of the T cell antigen receptor. Nature 314:631, (1985).

    Article  ADS  Google Scholar 

  22. J. Ritz, T. J. Campen, R. E. Schmidt, H. D. Royer, T. Hercend, R. E. Hussey, and E. L. Reinherz. Analysis of T-cell receptor gene rearrangement and expression in human natural killer cell clones. Science 228:1540, (1985).

    Article  ADS  Google Scholar 

  23. T. Hercend, S. C. Meuer, A. Brennan, M. A. Edson, O. Acuto, E. L. Reinherz, S. F. Schlossman, and J. Ritz. Identification of a clonally restricted 90 KID heterodimer on two cloned natural killer cell lines: its role cytotoxic effector function. J. Exp. Med. 158:1547, (1983).

    Article  Google Scholar 

  24. C. W. Reynolds, M. Bonyhadi, R. B. Herberman, H. A. Young, and S. M. Hedrick. Lack of gene rearrangement and mRNA expression of the beta chain of the T cell receptor in spontaneous rat large granular lymphocyte leukemia lines. J. Exp. Med. 161:1249, (1985).

    Article  Google Scholar 

  25. H. A. Young, J. R. Ortaldo, R. B. Herberman, and C. W. Reynolds. Analysis of T cell receptors in highly purified rat and human large granular lymphocytes (LGL): Lack of functional 1.3 kb large granular lymphocytes (LGL): Lack of functional 1.3 kb β-chain mRNA. J. Immunol. 137:2701–2704, (1986).

    Google Scholar 

  26. H. Binz, M. Fenner, D. Frei, and H. Wigzell. Two independent receptors allow selective target lysis by T cell clones. J. Exp. Med. 157:1252, (1983).

    Article  Google Scholar 

  27. P. Allavena, A. Rambaldi, P. G. Palliocci, R. Della-Favera, and A. Mantovani. Immunolgical and genotype analysis of human large granular lymphocytes expansions. J. Leukocyte Biol. 38:59, (1985).

    Google Scholar 

  28. C. G. Brooks. Reversible induction of natural killer cell activity in clonal murine cytotoxic T lymphocytes. Nature 305:155, (1983).

    Article  ADS  Google Scholar 

  29. P. A. Henkart, P. J. Willard, C. W. Reynolds, and M.P. Henkart. Cytolytic activity of purified cytoplasmic granules from cytotoxic rat LGL tumors. J. Exp. Med. 160:75, (1984).

    Article  Google Scholar 

  30. C. W. Reynolds, E. W. Bere, and J. M. Ward. Natural killer activity in the rat. III. Characterization of transplantable large granular lymphocyte (LGL) leukemias in the F344 rat. J. Immunol. 132:534, (1984).

    Google Scholar 

  31. C. W. Reynolds, D. Reichardt, M. Henkart, P. Millard, and P. Henkart. Inhibition of NK and ADCC activity by antibodies against purified cytoplasmic granules from rat LGL tumors. J. Exp. Med. in press.

    Google Scholar 

  32. S. C. Wright, and B. Bonavida. Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity (CMC). I. Release of cytotoxic factors specific for NK-sensitive target cells (NKCF) during co-culture of NK effector cells with NK target cells. J. Immunol. 129:433, (1982).

    Google Scholar 

  33. J. R. Ortaldo, I. Bianca, and R. B. Herberman. Studies of human natural killer cytotoxic factor (NKCF); Characterization and analysis of its mode of action. In P. Henkart, E. Martz, eds. Mechanisms of Cell-Mediated Cytotoxicity. New York: Plenum. 203 pp (1985).

    Chapter  Google Scholar 

  34. I. Bianca, R. B. Herberman, and J. R. Ortaldo. Human natural killer cytotoxic factor. Natural Immunity Cell Growth Resul. 4:48, (1985).

    Google Scholar 

  35. J. E. Blalock, J. A. Georgiades, N. F. Langford, and H. M. Johnson. Purified human immune interferon has more potent anticellular activity than fibroblast or leukocyte interferon. Cell Immunol. 49:390, (1980).

    Article  Google Scholar 

  36. B. B. Aggarwal, W. J. Henzel, B. Moffat, W. J. Kohn, and R. N. Harkins. Primary structure of human lymphotoxin derived from 1788 lymphoblastoid cell line. J. Biol. Chem. 260:2334. (1985).

    Google Scholar 

  37. E. A. Carswell, L. J. Old, R. L. Kassel, S. Green, N. Fiore, and N. Williamson. An endotoxin-induced serum factor that causes necrosis of tumors. Proc. Natl. Acad. Sci. USA 72:P3666. (1975).

    Article  ADS  Google Scholar 

  38. D. Pennica, G. W. Nedwin, J. S. Hayflick, P. H. Seeburg, R. Derynck, M. A. Paladino, W. J. Kohr, B. B. Aggarwal, and D. V. Goeddel. Human tumor necrosis factor: Precursor structure, expression and homology to lymphotoxin. Nature 312:724, (1984).

    Article  ADS  Google Scholar 

  39. J. H. Ransom, C. H. Evans, R. P. McCabe, N. Pomato, J. A. Heinbaugh, M. Chin, and M. G. Hanna Jr. Leukoregulin, a direct-acting anticancer immunological hormone that is distinct from lymphotoxin and interferon. Cancer Res. 45:851, (1985).

    Google Scholar 

  40. O. Stutman, C. J. Paige, and E. F. Figarella. Natural cytotoxic cells against solid tumors in mice. I. Strain and age distribution and target cell susceptibility. J. Immunol. 121:1819, (1978).

    Google Scholar 

  41. J. R. Ortaldo, L. H. Mason, B. J. Mathieson, S. M. Liang, D. A. flick, and R. B. Herberman. Mediation of mouse natural cytotoxic (NC) activity by tumor necrosis factor (TNF). Nature in press.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pittsburgh Cancer Institute and Departments of Medicine and Pathology, University of Pittsburgh, Pittsburgh, PA, 15213, USA

    Ronald B. Herberman

Authors
  1. Ronald B. Herberman
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of California, Irvine, California, USA

    Sudhir Gupta

  2. National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

    William E. Paul  & Anthony S. Fauci  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1987 Plenum Press, New York

About this chapter

Cite this chapter

Herberman, R.B. (1987). Activation of Natural Killer (NK) Cells and Mechanism of Their Cytotoxic Effects. In: Gupta, S., Paul, W.E., Fauci, A.S. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation. Advances in Experimental Medicine and Biology, vol 213. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5323-2_27

Download citation

  • DOI: https://doi.org/10.1007/978-1-4684-5323-2_27

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4684-5325-6

  • Online ISBN: 978-1-4684-5323-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation