Skip to main content
Log in

Regulation of natural killer activity

  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Cells mediating natural killer (NK) activity mediate lysis against a variety of tumor cells and may serve as important effector cells in host resistance to infection. NK active cells are present in virtually all individuals and can be rapidly activated by a wide range of stimuli. Their activities are non-MHC restricted and do not depend on sensitization by antigens, a prerequisite for specific immunity. Several important components of the immunoregulation of NK active cells are: 1) positive or negative signals that regulate the expression of NK activity, and 2) the ability of these cells to function as immunoregulatory cells. The majority of the agents that activate NK activity fall into two basic categories; the interferons and interleukin-2. This review will concentrate on studies regarding these two agents, and will primarily discuss the results obtained with recombinant molecules.

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. Herberman RB, Holden HT: Natural cell-mediated immunity. Adv Cancer Res 27: 305–377, 1978

    Google Scholar 

  2. Herberman RB, Ortaldo JR: Natural killer cells: Their role in defenses against disease. Science (Wash DC) 214: 24–30, 1981

    Google Scholar 

  3. Ortaldo JR, Herberman RB: Heterogeneity of natural killer cells. In: Paul WE, Fathman CG, Metzger H (eds) Annual Review of Immunology. Annual Review, Inc., Palo Alto, CA, 1984, pp 359–94

    Google Scholar 

  4. Itoh K, Tilden AB, Kumagai K, Balch CM: Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL-2)-induced activated killer (AK) cells. J Immunol 134: 802–807, 1985

    Google Scholar 

  5. Phillips JH, Lanier LL: Dissection of the lymphokine-activated killer phenomenon: Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med 136: 1579–1585, 1986

    Google Scholar 

  6. Ortaldo JR, Mason A, Overton R: Lymphokine-activated killer (LAK) cells: Analysis of progenitors and effectors. J Exp Med 164: 1193–1205, 1986

    Google Scholar 

  7. Herberman RB: Natural Cell-Mediated Immunity Against Tumors. Academic Press, New York, 1980

    Google Scholar 

  8. Welsh RM: Natural killer cells and interferon. CRC Crit Rev Immunol 5: 55–93, 1985

    Google Scholar 

  9. Trinchieri G, Santoli D, Dee RR, Knowles BB: Antiviral activity by culturing lymphocytes with tumor-derived or virus transformed cells: Identification of the antiviral activity as interferon and characterization of the human effector lymphocyte subpopulation. J Exp Med 147: 1229–1231, 1978

    Google Scholar 

  10. Cudkowicz G, Hochman PS: Do natural killer cells engage in regulated reactions against self to ensure homeostasis. Immunol Rev 44: 13–41, 1979

    Google Scholar 

  11. Stutman O, Lattime E: Lymphokines and natural cell-mediated cytotoxicity. In: Landy T (ed) Lymphokines. Academic Press, New York, 1985, pp 107–125

    Google Scholar 

  12. Herberman RB: Updated formulation and possible effector mechanisms. In: Yamamura Y, Tada T (eds) Progress in Immunology C. Fifth International Congress of Immunology. Academic Press, Orlando, 1983, pp 1157–1168

    Google Scholar 

  13. Timonen T, Ortaldo JR, Herberman RB: Characteristics of human large granular lymphocytes and relationship to natural killer and K cells. J Exp Med 153: 569–582, 1981

    Google Scholar 

  14. Ortaldo JR, Sharrow SO, Timonen T, Herberman RB: Determination of surface antigens on highly purified human NK cells by flow cytometry with monoclonal antibodies. J Immunol 121: 304–315, 1978

    Google Scholar 

  15. Kumagai K, Itoh K, Suzuki R, Hinuma S, Saitoh F: Studies of murine large granular lymphocytes. I. Identification of effector cells in NK and K cytotoxicities. J Immunol 129: 388–394, 1982

    Google Scholar 

  16. Wiltrout RH, Mathieson BJ, Talmadge JE, Reynolds CW, Xhang SR, Herberman RB, Ortaldo JR: Augmentation of organ-associated natural killer activity by biological response modifiers: Isolation and characterization of large granular lymphocytes from the liver. J Exp Med 160: 1431–1449, 1984

    Google Scholar 

  17. Reynolds CW, Timonen T, Herberman RB: Natural killer (NK) cell activity in the rat. I. Isolation and characterization of the effector cells. J Immunol 127: 6351–6362, 1981

    Google Scholar 

  18. Lanier LL, Le AM, Civin CI, Liken MR, Phillips JG: The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol 136: 4480–4486, 1986

    Google Scholar 

  19. Hercend T, Griffin JD, Bensussan A, Schmidt RE, Edson MA, Brennan A, Murray C, Ritz J: Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest 75: 932–943, 1985

    Google Scholar 

  20. Lanier LL, Kipps TJ, Phillips JH: Functional properties of a unique subset of cytotoxic CD3+ T lymphocytes that express Fc receptors for IgG (CD16/Leu-11 antigen). J Exp Med 162: 2089–2106, 1985

    Google Scholar 

  21. Allavena P, Ortaldo JR: Characteristics of human NK clones: Target specificity and phenotype. J Immunol 132: 2363–2399, 1984

    Google Scholar 

  22. Bolhuis RL, van de Gried RJ, Ronteltap CPM: Clonal expansion of human B73.1-positive natural killer cells or large granular lymphocytes exerting strong antibody-dependent and independent cytotoxicity and occasionally lectin-dependent cytotoxicity. Nat Immun Cell Growth Regul 3: 61–72, 1983

    Google Scholar 

  23. Bolhuis RL, van de Griend RJ: Phytohemagglutinin-induced proliferation and cytolytic activity in T3+ but not in T3- cloned T lymphocytes requires the involvement of the T3 antigen for signal transmission. Cell Immunol 93: 46–57, 1985

    Google Scholar 

  24. Stutman O, Lattime EC, Figarella EF: Natural cytotoxic cells against solid tumors in mice: A comparison with natural killer cells. Fed Proc 40: 2699–2704, 1981

    Google Scholar 

  25. Clark EA, Russel RH, Egghart M, Horton MA: Characteristics and genetic control of NK-cell-mediated cytotoxicity by naturally acquired infection in the mouse. Adv Cancer Res 27: 305–311, 1979

    Google Scholar 

  26. Roder J, Duwe A: The beige mutation in the mouse selectively impairs natural killer cell function. Nature 278: 451–452, 1979

    Google Scholar 

  27. Henney CS, Tracey D, Durdik JM, Klimpel G: Natural killer cellsin vitro andin vivo. Am J Pathol 93: 459–475, 1978

    Google Scholar 

  28. Djeu JY, Heinbaugh JA, Holden HT, Herberman RB: Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol 122, 175–181, 1979

    Google Scholar 

  29. Ortaldo JR, Mason A, Rehberg E, Moschena J, Kelder B, Pestka S, Herberman RB: Effects of recombinant and hybrid recombinant human leukocyte interferons on cytotoxic activity of natural killer cells. J Biol Chem 258: 1501–1511, 1983

    Google Scholar 

  30. Ortaldo JR, Phillips W, Wasserman K, Herberman RB: Effects of metabolic inhibitors on spontaneous and interferon-boosted natural killer cell activity. J Immunol 125: 1839–1845, 1980

    Google Scholar 

  31. Schmidt A, Crisp B, Krause D, Silverman RH, Herberman RB, Ortaldo JR: Involvement of the 2′–5′ A pathway in the augmentation of natural killer activity. Nat Immun Cell Growth Regul 6: 19–27, 1987

    Google Scholar 

  32. Koren HS, Anderson SJ, Fischer DG, Copeland CS, Jenson PJ: Regulation of human natural killing. I. Role of monocytes, interferon, and prostaglandins. J Immunol 127: 2007–2015, 1981

    Google Scholar 

  33. Trinchieri G, Santoli D: Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Enhancement of natural killer activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J Exp Med 147: 1314–1322, 1978

    Google Scholar 

  34. Ortaldo JR, Herberman RB: Augmentation of natural killer activity. In: Lotzova E, Herberman RB (eds) Immunobiology of Natural Killer Cells, Vol. II. CRC Press, Boca Raton, 1986, pp 145–162

    Google Scholar 

  35. Sayers TJ, Mason AT, Ortaldo JR: Regulation of human natural killer cell activity by interferon-g: Lack of a role in interleukin 2-mediated augmentation. J Immunol 136: 2176–2180, 1986

    Google Scholar 

  36. Weigent DA, Stanton GJ, Johnson HM: Interleukin 2 enhances natural killer activity through induction of gamma-interferon. Infect Immun 41, 992–997, 1983

    Google Scholar 

  37. Kawase I, Brooks CG, Kuribayashi K, Otabuenaga S, Newman W, Gillis S, Henney CS: Interleukin 2 induces gamma-interferon production: Participation of macrophages and NK-like cells. J Immunol 131: 288–292, 1983

    Google Scholar 

  38. Ortaldo JR, Mason AT, Gerard JP, Henderson LE, Farrar W, Hopkins RF III, Herberman RB, Rabin H: Effects of natural and recombinant IL-2 on regulation of IFNγ production and natural killer activity: Lack of involvement of the Tac antigen for these immunoregulatory effects. J Immunol 133: 779–792, 1984

    Google Scholar 

  39. Grimm EA, Ramsey KM, Mazumder A, Wilson DJ, Djeu JY, Rosenberg SA: Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymusderived lymphocytes, and natural killer cells. J Exp Med 157: 884–897, 1983

    Google Scholar 

  40. Yamada S, Ruscetti FW, Overton WR, Herberman RB, Birchenall-Sparks MC, Ortaldo JR: Regulation of human large granular lymphocyte and T cell growth and function by recombinant interleukin 2. I. Induction of interleukin 2 receptor and promotion of growth of cells with enhanced cytotoxicity. J Leuk Biol, in press, 1987

  41. Teshigawara K, Wang HM, Kato K, Smith KA: Interleukin 2 high-affinity receptor expression requires two distinct binding proteins. J Exp Med 165: 223–238, 1987

    Google Scholar 

  42. Herman J, Dinarello CA, Kew MC, Rabson AR: The role of interleukin 1 (IL 1) in tumor-NK cell interactions: Correction of defective NK cell activity in cancer patients by treating target cells with IL 1. J Immunol 135: 2882–2886, 1985

    Google Scholar 

  43. Scala G, Djeu JY, Allavena P, Kasahara T, Ortaldo JR, Herberman RB, Oppenheim JJ: Cytokine secretion and noncytotoxic functions of human large granular lymphocytes. In: Lotzova E, Herberman RB (eds) Immunobiology of Natural Killer Cells, Vol. II. CRC Press, Boca Raton, 1986, pp 133–144

    Google Scholar 

  44. Djeu JY, Stocks N, Zoon K, Stanton GJ, Timonen T, Herberman RB: Production of interferon by human large granular lymphocytes upon exposure to influenza and herpes viruses. J Exp Med 156: 1222–1227, 1982

    Google Scholar 

  45. Lang NP, Ortaldo JR, Bonnard GD, Herberman RB: Effects of interferon and prostaglandins on human natural and lectin-induced cytotoxicity. J Natl Cancer Inst 69: 339–345, 1982

    Google Scholar 

  46. Kendall RA, Targan S: The dual effect of prostaglandin and ethanol on the natural killer cytolytic process: Effector activation and NK-target cell conjugate lytic inhibition. J Immunol 125: 2770–2779, 1981

    Google Scholar 

  47. Brunda MJ, Herberman RB, Holden HT: Inhibition of murine natural killer cell activity by prostaglandins. J Immunol 124: 2682–2690, 1980

    Google Scholar 

  48. Herberman RB, Reynolds CW, Ortaldo JR: Mechanism of cytotoxicity by natural killer (NK) cells. Annu Rev Immunol 4: 651–680, 1986

    Google Scholar 

  49. Hamilton TC, Young RC, Louie KG, Behrens BC, McKoy WM, Grotzinger KR, Ozols RV: Characterization of a human ovarian carcinoma cell line (NIH: OVCAR-3) with androgen and estrogen receptors. Cancer Res 43: 5370–5389, 1984

    Google Scholar 

  50. Ortaldo JR, Porter HR, Miller P, Stevenson HC, Ozols RF, Hamilton TC: Adoptive cellular immunotherapy of human ovarian carcinoma xenografts in nude mice. Cancer Res 46: 4414–4419, 1986

    Google Scholar 

  51. Mazumder A, Eberlein TJ, Grimm EJ: Phase I study of the adoptive immunotherapy of human cancer with lectin activated autologous mononuclear cells. Cancer 53: 896–905, 1984

    Google Scholar 

  52. Myers C: The use of intraperitoneal chemotherapy in the treatment of ovarian cancer. Semin Oncol 11: 275–284, 1984

    Google Scholar 

  53. Dedrick RL: Theoretical and experimental bases of intraperitoneal chemotherapy. J Exp Med 155: 1823–1831, 1982

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ortaldo, J.R. Regulation of natural killer activity. Cancer Metast Rev 6, 637–651 (1987). https://doi.org/10.1007/BF00047471

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00047471

Key words

Navigation