Skip to main content
SpringerLink
Log in

The biology of the human natural killer cell

  • Special Article
  • Published:
Journal of Clinical Immunology Aims and scope Submit manuscript

Abstract

Natural killer (NK) cells in the human are a population of large granular lymphocytes (LGL) with at least one unique surface antigen not expressed on cells of other lineages. NK-target-cell interaction appears to involve carbohydrate recognition and, following binding, the NK cells are induced to generate O2 −, transmethylate membrane phospholipids, and activate phospholipase A2. Some or all of these activities trigger a cascade of events which ultimately leads to the secretion of a substance toxic to the target cell. A variety of genes controls various steps in this cytolytic pathway. There is a good deal of evidence in the mouse, and some in the human, that NK cells play a role in host surveillance against tumor development, resistance to viral infections, and, possibly, hematopoietic regulation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Pross HF, Jondal M: Cytotoxic lymphocytes from normal donors. A functional marker of human non-T lymphocytes. Clin Exp Immunol 21:226–235, 1975

    Google Scholar 

  2. Herberman RB, Nunn ME, Holden HT, Lavrin DH: Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int J Cancer 16:230–239, 1975

    Google Scholar 

  3. Kiessling R, Klein E, Wigzell H: Natural killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype. Eur J Immunol 5:112–117, 1975

    Google Scholar 

  4. Pross HF, Baines MG: Spontaneous human lymphocytemediated cytotoxicity against tumor target cells. VI. A brief review. Cancer Immunol Immunother 3:75–85, 1977

    Google Scholar 

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

    Google Scholar 

  6. Herberman RB, Djeu JY, Kay HD, Ortaldo JR, Riccardi C, Bonnard GD, Holden HT, Fagnani R, Santoni A, Puccetti P: Natural killer cells: Characteristics and regulation of activity. Immunol Rev 44:43–70, 1979

    Google Scholar 

  7. Toivanen P, Uksila J, Leino A, Lassila O, Hirvonen T, Ruuskanen O: Development of mitogen responding T cells and natural killer cells in the human fetus. Immunol Rev 57:89–105, 1981

    Google Scholar 

  8. Baines MG, Pross HF, Millar KG: Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IV. The suppressive effect of normal pregnancy. Am J Obstet Gynecol 130:741–744, 1978

    Google Scholar 

  9. Haller O, Kiessling R, Orn A, Wigzell H: Generation of natural killer cells: An autonomous function of the bone marrow. J Exp Med 145:1411–1416, 1977

    Google Scholar 

  10. Pross HF, Baines MG: Studies of human natural killer cells. I.In vivo parameters affecting normal cytotoxic function. Int J Cancer 29:383–390, 1982

    Google Scholar 

  11. Fernandes G, Gupta S: Natural killing and antibody-dependent cytotoxicity by lymphocyte subpopulations in young and aging humans. J Clin Immunol 1:141–148, 1981

    Google Scholar 

  12. Penschow J, MacKay IR: NK and K cell activity of human blood: differences according to sex, age, and disease. Ann Rheum Dis 39:82–86, 1980

    Google Scholar 

  13. Bloom ET: Lymphocytes from children and infants mediate natural cell mediated cytotoxicity. Cancer Immunol Immunother 10:261–263, 1981

    Google Scholar 

  14. Antonelli P, Stewart W, Dupont B: Distribution of natural killer cell activity in peripheral blood, cord blood, thymus, lymph nodes, and spleen and the effect ofin vivo treatment with interferon preparation. Clin Immunol Immunopathol 19:161–169, 1981

    Google Scholar 

  15. Nagel JE, Collins GD, Adler WH: Spontaneous or natural killer cytotoxicity of K562 erythroleukemic cells in normal patients. Cancer Res 41:2284–2288, 1981

    Google Scholar 

  16. Forbes JT, Niblack GD, Fuchs R, Richie RE, Johnson HK, Oldham RK: Human Natural Cell-mediated Cytotoxicity. I. Levels in peripheral blood, cord blood, and thoracic duct lymphocytes. Cancer Immunol Immunother 11:139–145, 1981

    Google Scholar 

  17. Targan SR, Gale RP, Jondal M: Bone marrow modulation of spontaneous killer cellular cytotoxicity (SKCC) induction. J Clin Lab Immunol 4:1–6, 1980

    Google Scholar 

  18. Timonen T, Ranki A, Saksela E, Hayry P: Fractionation, morphological and functional characterization of effector cells responsible for human natural killer activity against cell-line targets. Cell Immunol 48:121–132, 1979

    Google Scholar 

  19. Timonen T, Saksela E: Isolation of human natural killer cells by density gradient centrifugation. J Immunol Methods 36:285–291, 1980

    Google Scholar 

  20. 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 

  21. Abo T, Balch CM: A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol 127:1024–1029, 1981

    Google Scholar 

  22. Livnat S, Seigneuret M, Storb R, Prentice RL: Analysis of cytotoxic effector cell function in patients with leukemia or aplastic anemia before and after marrow transplantation. J Immunol 124:481–490, 1980

    Google Scholar 

  23. Nieminen P, Paasivuo R, Saksela E: Effect of a monoclonal anti-large granular lymphocyte antibody on the human NK activity. J Immunol 128:1097–1101, 1982

    Google Scholar 

  24. Breard J, Reinherz EL, O'Brien C, Schlossman SF: Delineation of an effector population responsible for natural killing and antibody dependent cellular cytotoxicity in man. Clin Immunol Immunopathol 17:145–151, 1980

    Google Scholar 

  25. Breard J, Reinherz EL, Kung PC, Goldstein G, Schlossman SF: A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol 124:1943–1948, 1980

    Google Scholar 

  26. Zarling JM, Kung PC: Monoclonal antibodies which distinguish between human NK and cytotoxic T lymphocytes. Nature 288:394–396, 1980

    Google Scholar 

  27. Ault KA, Springer TA: Cross reaction of a rat anti-mouse phagocyte specific monoclonal antibody (anti-Mac-1) with human monocytes and natural killer cells. J Immunol 126:359–364, 1981

    Google Scholar 

  28. Todd RF, Nadler LM, Schlossman SF: Antigens on human monocytes identified by monoclonal antibodies. J Immunol 126:1435–1442, 1981

    Google Scholar 

  29. Roder JC, Todd RF, Rubin P, Haliotis T, Helfand S, Werkmeister J, Pross HF, Boxer L, Schlossman SF, Fauci AS: The Chediak-Higashi gene in humans. III. Studies on the mechanism of NK impairment (submitted for publication)

  30. Ranki A: Nonspecific esterase activity in human lymphocytes. Histochemical characterization and distribution among major lymphocyte subclasses. Clin Immunol Immunopathol 10:47–52, 1978

    Google Scholar 

  31. 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 127:2401–2409, 1981

    Google Scholar 

  32. Janossy G, Tidman N, Papageorgiou ES, Kung PC, Goldstein G: Distribution of T lymphocyte subsets in the human bone marrow and thymus: an analysis with monoclonal antibodies. J Immunol 126:1608–1613, 1980

    Google Scholar 

  33. Haynes BF, Mann DL, Katz P, Eisenbarth GS, Himmler M, Strominger JL, Fauci AS: Use of a monoclonal antibody (3Al) to characterize functional human T cell subsets. Clin Res 28:348, 1980 (abstract)

    Google Scholar 

  34. Roder JC, Kiessling R: Target-effector interaction in the natural killer cell system. I. Co-variance and genetic control of cytolytic and target-cell-binding subpopulations in the mouse. Scand J Immunol 8:135–144, 1978

    Google Scholar 

  35. Roder JC, Kiessling R, Biberfeld P, Andersson B: Target-effector interaction in the natural killer (NK) cell system. II. The isolation of NK cells and studies on the mechanism of killing. J Immunol 121:2509–2517, 1978

    Google Scholar 

  36. Roder JC, Argov S, Klein M, Petersson C, Kiessling R, Andersson K, Hansson M: Target-effector interaction in the natural killer cell system. V. Energy requirements, membrane integrity, and the possible involvement of lysosomal enzymes. Immunology 40:107–116, 1980

    Google Scholar 

  37. Granger G, Kolb W: Lymphocytein vitro cytotoxicity: Mechanisms of immune and non-immune small lymphocyte-mediated target L cell destruction. J Immunol 101:111–120, 1968

    Google Scholar 

  38. Henney CS: T-cell-mediated cytolysis: An overview of some current issues.In Contemporary Topics in Immunobiology, O Stutman (ed). New York, Plenum Press, 1977, pp 245–277

    Google Scholar 

  39. Roder JC, Karre K, Kiessling R: Natural killer cells. Prog Allergy 28:66–159, 1981

    Google Scholar 

  40. Carpen O, Virtanen I, Saksela E: The cytotoxic activity of human natural killer cells requires an intact secretory apparatus. Cell Immunol 58:97–106, 1981

    Google Scholar 

  41. Saksela E, Timonen T, Ranki A, Hayry P: Morphological and functional characterization of isolated effector cells responsible for human natural killer activity to fetal fibroblasts and to cultured cell line targets. Immunol Rev 44:71–123, 1979

    Google Scholar 

  42. Ullberg M, Jondal M: Recycling and target binding capacity of human natural killer cells. J Exp Med 153:615–628, 1981

    Google Scholar 

  43. Targan S, Dorey F: Interferon activation of “pre-spontaneous killer” (Pre-SK) cells and alteration in kinetics of lysis of both “pre-SK” and active SK cells. J Immunol 124:2157–2161, 1980

    Google Scholar 

  44. Roder JC, Helfand JC, Werkmeister J, McGarry R, Beaumont TJ, Duwe A: Oxygen intermediates are triggered early in the cytolytic pathway of human NK cells. Nature (in press), 1982

  45. Helfand SL, Werkmeister J, Roder JC: The chemiluminescence response of human NK cells. I. The relationship between target cell binding, chemiluminescence and cytolysis. J Exp Med (in press), 1982

  46. Roder JC, Klein M: Target-effector interaction in the natural killer cell system. IV. Modulation by cyclic nucleotides. J Immunol 123:2785–2790, 1979

    Google Scholar 

  47. Katz P, Zaytoun AM, Fauci AS: Mechanism of human cell-mediated cytotoxicity. I. Modulation of natural killer cell activity by cyclic nucleotides. J Immunol (in press), 1982

  48. Tovey MG, Rochette-Egly C, Castagna M: Effect of interferon on concentrations of cyclic nucleotides in cultured cells. Proc Natl Acad Sci USA 76:3890–3893, 1979

    Google Scholar 

  49. Katz P, Roder JC, Zaytoun AM, Herberman RB, Fauci AS: Mechanism of human cell-mediated cytotoxicity. II. Correction of the selective defect in natural killing in the Chediak-Higashi syndrome with inducers of intracellular cyclic GMP. J Immunol (in press), 1982

  50. Roder JC, Laing L, Haliotis T, Kozbor D: Genetic control of human NK function.In NK Cells: Fundamental Aspects and Role in Cancer, Human Cancer Immunology, Vol 6, RB Herberman (ed). Amsterdam, North-Holland (in press), 1982

    Google Scholar 

  51. Hoffman T, Hirata F, Bougnoux P, Fraser BA, Goldfarb RH, Herberman RB, Axelrod J: Phospholipid methylation and phospholipase A2 activation in cytotoxicity by human natural killer cells. Proc Natl Acad Sci USA 78:3839–3843, 1981

    Google Scholar 

  52. Hirata F, Axelrod J: Phospholipid methylation and biological signal transduction. Science 209:1082–1090, 1980

    Google Scholar 

  53. Quan PC, Ishizaka T, Bloom BR: Studies on the mechanism of NK cell lysis. J Immunol 128:1786–1791, 1982

    Google Scholar 

  54. Neighbour AP, Huberman HS: Sr++ induced inhibition of human natural killer (NK) cell-mediated cytotoxicity. J Immunol 128:1236–1240, 1982

    Google Scholar 

  55. Weissman G, Goldstein F, Hoffstein S, Tsung PK: Reciprocal effects of cAMP and cGMP on microtubule dependent release of lysosomal enzymes. Ann NY Acad Sci 253:750–762, 1975

    Google Scholar 

  56. Forbes JT, Bretthauer RK, Oeltmann TN: Mannose 6-, fructose 1- and fructose 6-phosphates inhibit human natural cell-mediated cytotoxicity. Proc Natl Acad Sci USA 78:5797–5801, 1981

    Google Scholar 

  57. Brandt EJ, Swank RT, Novack EK: The murine Chediak-Higashi mutation and other murine pigmentation mutations.In Immunologic Defects in Laboratory Animals I, ME Gershwin, B Merchant (eds). New York, Plenum Press, 1980, pp 99–117

    Google Scholar 

  58. Abo T, Roder JC, Abo W, Cooper MD, Balch CM: NK (HNK-1+) cells in Chediak-Higashi patients are present in normal numbers but are abnormal in function and morphology. J Clin Invest (in press), 1982

  59. Roder JC, Haliotis T, Klein M, Korec S, Jett J, Ortaldo J, Herberman RB, Katz P, Fauci AS: A new immunodeficiency disorder in humans involving NK cells. Nature 284:553–555, 1980

    Google Scholar 

  60. Haliotis T, Roder JC, Klein M, Ortaldo J, Fauci AS, Herberman RB: Chediak-Higashi gene in humans. I. Impairment of natural killer function. J Exp Med 151:1029–1058, 1980

    Google Scholar 

  61. Wright SC, Bonavida B: Selective lysis of NK sensitive target cells by a soluble mediator released from murine spleen cells and human peripheral blood lymphocytes. J Immunol 126:1516–1521, 1981

    Google Scholar 

  62. Roder JC, Beaumont TJ, Kerbel RS, Haliotis T, Kozbor D: Selective natural killer resistance in a clone of YAC lymphoma cells. Proc Natl Acad Sci USA 78:6396–6400, 1981

    Google Scholar 

  63. Stutman O, Dien P, Wisun R, Lattime E: Natural cytotoxic cells against solid tumors in mice: Blocking of cytotoxicity by D-mannose. Proc Natl Acad Sci USA 77:2895–2898, 1980

    Google Scholar 

  64. Dennert G, Yogeeswaran G, Yamagata S: Cloned cell lines with natural killer activity. Specificity, function and cell surface markers. J Exp Med 153:545–556, 1981

    Google Scholar 

  65. Piontek GE, Gronberg A, Ahrlund-Richter L, Kiessling R: NK-patterned binding expressed by non-NK mouse leukocytes. Int J Cancer (in press), 1982

  66. Roder JC, Ahrlund-Richter L, Jondal M: Target-effector interaction in the human and murine natural killer system. Specificity and xenogeneic reactivity of solubilized natural killer-target structure complex and its loss in a somatic cell hybrid. J Exp Med 150:471–481, 1979

    Google Scholar 

  67. Roder JC, Rosen A, Fenyo EM, Troy FA: Target-effector interaction in the natural killer cell system. The isolation of target structures. Proc Natl Acad Sci USA 76:1405–1409, 1979

    Google Scholar 

  68. Rubin P, Pross HF, Roder JC: Studies of human natural killer cells. II. Analysis at the single cell level. J Immunol 128:2553–2558, 1982

    Google Scholar 

  69. Phillips WH, Ortaldo JR, Herberman RB: Selective depletion of human natural killer cells on monolayers of target cells. J Immunol 125:2322–2327, 1980

    Google Scholar 

  70. Takasugi M, Akira D, Takasugi J, Mickey M: Specificities of human cell mediated cytotoxicity. J Natl Cancer Inst 59:69–75, 1977

    Google Scholar 

  71. Jensen PJ, Koren HS: Depletion of NK by cellular immunoadsorption. J Immunol 123:1127–1132, 1979

    Google Scholar 

  72. Callewaert DM, Lightbody JJ, Kaplan J, Jaroszewski J, Peterson WD, Rosenberg JC: Spontaneous cytotoxicity of cultured human cell lines mediated by normal PBL. II. Specificity for target antigens. Cell Immunol 42:103–112, 1979

    Google Scholar 

  73. Hansson M, Karre K, Bakas T, Kiessling R, Klein G: Intra- and interspecies reactivity of human and mouse natural killer (NK) cells. J Immunol 121:6–12, 1979

    Google Scholar 

  74. Hansson M, Kiessling R, Andersson B, Karre K, Roder JC: NK cell sensitive T-cell subpopulations in thymus: Inverse correlation to host NK activity. Nature 278:174, 1979

    Google Scholar 

  75. Hansson M, Karre K, Kiessling R, Roder JC, Andersson B, Hayry P: Natural NK-cell targets in the mouse thymus: Characteristics of the sensitive cell population. J Immunol 123:765–771, 1979

    Google Scholar 

  76. Ono A, Amos DB, Koren HS: Selective cellular natural killing against human leukaemic T cells and thymus. Nature 266:546–548, 1977

    Google Scholar 

  77. Stern P, Gidlund M, Orn A, Wigzell H: Natural killer cells mediate lysis of embryonal carcinoma cells lacking MHC. Nature 285:341–342, 1980

    Google Scholar 

  78. Gidlund M, Orn A, Pattengale PK, Jansson M, Wigzell H, Nilsson K: Natural killer cells kill tumor cells at a given stage of differentiation. Nature 292:848–850, 1981

    Google Scholar 

  79. Werkmeister J, Helfand S, Haliotis T, Rubin P, Pross H, Roder JC: Tumor cell differentiation modulates susceptibility to natural killer cells. Cell Immunol 69:122–127, 1982

    Google Scholar 

  80. Karre K: On the immunobiology of natural killer cells. Studies of murine NK cells and their interactions with T cells and T lymphomas, PhD thesis. Stockholm, Sweden, Karolinska Institute, 1981

    Google Scholar 

  81. Gronberg A, Kiessling R, Eriksson E, Hansson M: Variants from a MLV-induced lymphoma selected for decreased sensitivity to NK lysis. J Immunol 127:1734–1739, 1981

    Google Scholar 

  82. Durdik JM, Beck BN, Clark EA, Henney CS: Characterization of a lymphoma cell variant selectively resistant to natural killer cells. J Immunol 125:683–688, 1980

    Google Scholar 

  83. Yogeeswaran G, Gronberg A, Hansson M, Dalianis T, Kiessling R, Welsh RM: Correlation of glycosphingolipids and sialic acid in YAC-1 lymphoma variants with their sensitivity to natural killer-cell-mediated lysis. Int J Cancer 28:517–526, 1981

    Google Scholar 

  84. Young WW, Durdik JM, Urdal D, Hakomori SI, Henney CS: Glycolipid expression in lymphoma cell variants: Chemical quantity, immunologic reactivity, and correlations with susceptibility to NK cells. J Immunol 126:1–6, 1981

    Google Scholar 

  85. Baines MG, Lafleur FL, Holbein BE: Human natural killer (NK) cell associated transferrin mediates the NK effector: Target interaction with K562 tumor cells (submitted for publication)

  86. Trowbridge IS, Omary MB: Human cell surface glycoprotein related to cell proliferation is the receptor for transferrin. Proc Natl Acad Sci USA 78:3039–3043, 1981

    Google Scholar 

  87. Sutherland R, Delia D, Schneider C, Newman R, Kemshead J, Greaves M: Ubiquitous cell-surface glycoprotein on tumor cells is proliferation associated receptor for transferrin. Proc Natl Acad Sci USA 78:4515–4519, 1981

    Google Scholar 

  88. Herberman RB, Ortaldo JR, Bonnard GD: Augmentation by interferon of human natural and antibody dependent cell-mediated cytotoxicity. Nature 277:221–223, 1979

    Google Scholar 

  89. Trinchieri G, Santoli D: Enhancement of human natural killer cell activity by interferon. J Immunol 120:1845–1850, 1978

    Google Scholar 

  90. Saksela E, Timonen T, Cantell K: Human natural killer cell activity is augmented by interferon via recruitment of “pre-NK” cells. Scand J Immunol 10:257–266, 1979

    Google Scholar 

  91. Ortaldo JR, Phillips W, Wasserman K, Herberman RB: Effects of metabolic inhibitors on spontaneous and interferon-boosted human natural killer cell activity. J Immunol 125:1839–1844, 1981

    Google Scholar 

  92. Friedman RM: Antiviral activity of interferons. Bacteriol Rev 41:543–567, 1977

    Google Scholar 

  93. Gidlund M, Orn A, Wigzell H, Senik A, Gresser I: Enhanced NK activity in mice injected with interferon and interferon inducers. Nature 273:759–761, 1978

    Google Scholar 

  94. Senik A, Kolb JP, Orn A, Gidlund M: Study of the mechanism forin vitro activation of mouse NK cells by interferon. Scand J Immunol 12:51–60, 1980

    Google Scholar 

  95. Virilizier JL, Lipinski M, Tursz T, Griscelli C: Defects in immune interferon secretion and natural killer activity in patients with immunological disorders. Lancet 2:696, 1979

    Google Scholar 

  96. Virilizier JL, Griscelli C: Interferon administration as an immunoregulatory and anti-microbial treatment in children with defective interferon secretion.In Primary Immunodeficiencies, M Seligmann, W Hitzig (eds), New York, Elsevier/North-Holland Biomedical Press, 1980, pp 473–484

    Google Scholar 

  97. Welsh RM, Karre K, Hansson M, Kunkel L, Kiessling R: Interferon mediated protection of normal and tumor target cells against lysis by mouse natural killer cells. J Immunol 126:219–225, 1981

    Google Scholar 

  98. Wolfe SA, Tracey DE, Henney CS: Induction of “natural killer” cells by BCG. Nature 262:584–586, 1976

    Google Scholar 

  99. Timonen T, Saksela E, Virtanen I, Cantell K: Natural killer cells are responsible for the interferon production induced in human lymphocytes by tumor cell contact. Eur J Immunol 10:422–427, 1980

    Google Scholar 

  100. Seaman WE, Blackman MA, Gindhart TD, Roubinian JR, Loeb J, Talal N: B-Estradiol reduces natural killer cells in mice. J Immunol 121:2193–2198, 1978

    Google Scholar 

  101. Droller MJ, Schneider MU, Perlmann P: A possible role of prostaglandins in the inhibition of natural and antibody-dependent cell-mediated cytotoxicity against tumor cells. Cell Immunol 39:165–177, 1978

    Google Scholar 

  102. Parrillo JE, Fauci AS: Comparison of the effector cells in human spontaneous cellular cytotoxicity and antibody-dependent cellular cytotoxicity: differential sensitivity of effector cells toin vivo andin vitro corticosteroids. Scand J Immunol 8:99–107, 1978

    Google Scholar 

  103. 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 

  104. Henney CS, Kuribayashi K, Kern DE, Gillis S: Interleukin-2 augments natural killer cell activity. Nature 291:335–338, 1981

    Google Scholar 

  105. Roder JC, Duwe AK: The beige mutation in the mouse selectively impairs NK cell function. Nature 278:451–453, 1979

    Google Scholar 

  106. Clark E, Windsor NT, Sturge J, Stanton TH: Mutations that influence natural cell-mediated cytotoxicity in rodents.In Natural Cell Mediated Immunity Against Tumors, RB Herberman (ed). New York, Academic Press, 1980, pp 417–427

    Google Scholar 

  107. Santoli D, Trinchieri G, Zimjewski CM, Koprowski H: HLA-related control of spontaneous and antibody-dependent cell-mediated cytotoxic activity in humans. J Immunol 117:765–770, 1976

    Google Scholar 

  108. Petranyi G, Benczur M, Onody C, Hollan SR: HLA-3, 7 and lymphocyte cytotoxic activity. Lancet 1:736, 1974

    Google Scholar 

  109. Hersey P, Edwards A, Trilivas C, Shaw H, Milton GW: Relationship of natural killer-cell activity to Rhesus antigens in man. Br J Cancer 39:234–240, 1979

    Google Scholar 

  110. Hersey P, Edwards A, Honeyman M, McCarthy WH: Low natural-killer-cell activity in familial melanoma patients and their relatives. Br J Cancer 40:113–122, 1979

    Google Scholar 

  111. Helfand S, Werkmeister J, Roder J, Pross H, Abo T, Balch C: The chemiluminescence response of human NK cells. II. High and low NK responders differ at the level of early activation (submitted for publication)

  112. Mandeville R, Rocheleau N: Natural cell mediated cytotoxicity in normal human peripheral blood lymphocytes and itsin vitro boosting with BCG. Cancer Immunol Immunother (in press), 1982

  113. Pross HF, Baines MG, Rubin P, Shragge P, Patterson M: Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. Quantitation of natural killer (NK) cell activity. J Clin Immunol 1:51–63, 1981

    Google Scholar 

  114. Callewaert DM, Smeekens SP, Mahle NH: Improved quantification of cellular cytotoxicity reactions: Determination of kinetic parameters for natural cytotoxicity by a distribution-free procedure. J Immunol Methods 49:25–37, 1982

    Google Scholar 

  115. Klein M, Roder J, Haliotis T, Korec S, Jett J, Herberman RB, Katz P, Fauci AS: Chediak-Higashi gene in humans. II. The selectivity of the defect in natural-killer and antibody dependent cell-mediated cytotoxicity function. J Exp Med 151:1049–1058, 1980

    Google Scholar 

  116. Klein GO, Ramirez-Duque P, Merino F, Forsgren M, Henle W: Low natural killer cell activity and elevated antibody titers to Epstein-Barr virus in patients with Chediak-Higashi syndrome (submitted for publication)

  117. Sullivan JL, Byron KS, Brewster FF, Purtilo D: Deficient natural killer cell activity in X-linked lymphoproliferative syndrome. Science 210:543–545, 1980

    Google Scholar 

  118. Koren H, Amos B, Buckley R: Natural killing in immunodeficient patients. J Immunol 120:796–799, 1978

    Google Scholar 

  119. Lipinski M, Virilizier JL, Tursz T, Griscelli C: Natural killer and killer cell activities in patients with primary immunodeficiencies or defects in immune interferon production. Eur J Immunol 10:246–249, 1980

    Google Scholar 

  120. Pross HF, Gupta S, Good RA, Baines M: Spontaneous human lymphocyte mediated cytotoxicity against tumor target cells. VII. The effect of immunodeficiency disease. Cell Immunol 43:160–175, 1979

    Google Scholar 

  121. Nelson D: Lymphocyte-mediated cytotoxicity in immunodeficiency patients.In Primary Immunodeficiencies, M Seligmann, W Hitzic (eds). New York, Elsevier/North-Holland, 1980, pp 141–149

    Google Scholar 

  122. Pross HF, Baines MG: Spontaneous human lymphocyte-mediated cytotoxicity against tumour target cells. I. The effect of malignant disease. Int J Cancer 18:593–604, 1976

    Google Scholar 

  123. Takasugi M, Ramseyer A, Takasugi J: Decline of natural nonselective cell-mediated cytotoxicity in patients with tumor progression. Cancer Res 37:413–418, 1977

    Google Scholar 

  124. Forbes JT, Greco FA, Oldham RK: Human natural cell-mediated cytotoxicity. II. Levels in neoplastic disease. Cancer Immunol Immunother 11:147–153, 1981

    Google Scholar 

  125. Hersey P, Edwards A, Milton GW, McCarthy WH: Relationship of cell-mediated cytotoxicity against melanoma cells to prognosis in melanoma patients. Br J Cancer 37:505–514, 1978

    Google Scholar 

  126. DeBoer KP, Braun DP, Harris JE: Natural cytotoxicity and antibody-dependent cytotoxicity in solid tumor cancer patients: Regulation by adherent cells. Clin Immunol Immunopathol 23:133–144, 1982

    Google Scholar 

  127. Kadish AS, Doyle AT, Steinhauer EH, Ghossein NA: Natural cytotoxicity and interferon production in human cancer: Deficient natural killer activity and normal interferon production in patients with advanced disease. J Immunol 127:1817–1822, 1981

    Google Scholar 

  128. Cunningham-Rundles S, Filippa DA, Braun DW Jr, Antonelli P, Ashikari H: Natural cytotoxicity of peripheral blood lymphocytes and regional lymph node cells in breast cancer in women. J Natl Cancer Inst 67:585–590, 1981

    Google Scholar 

  129. Behelak U, Banerjee D, Richter M: Immunocompetent cells in patients with malignant disease. I. The lack of naturally occurring killer cell activity in the unfractionated circulating lymphocytes from patients with chronic lymphocytic leukemia (CLL). Cancer 38:2274–2277, 1976

    Google Scholar 

  130. Ziegler HW, Kay NE, Zarling JM: Deficiency of natural killer cell activity in patients with chronic lymphocytic leukemia. Int J Cancer 27:321–327, 1981

    Google Scholar 

  131. McGeorge MB, Russell EC, Mohanakumar T: Immunologic evaluation of long term effects of childhood ALL chemotherapy: Analysis ofin vitro NK- and K-cell activities of peripheral blood lymphocytes. Am J Hematol 12:19–27, 1982

    Google Scholar 

  132. Fernandes G, Garrett T, Nair M, Straus D, Good RA, Gupta S: Studies in acute leukemia. I. Antibody-dependent and spontaneous cellular cytotoxicity by leukemic blasts from patients with acute nonlymphoid leukemia. Blood 54:573–580, 1979

    Google Scholar 

  133. Siegal FP, Lopez C, Hammer GS, Brown AE, Kornfeld SJ, Gold J, Hasset J, Hirschman SZ, Cunningham-Rundles C, Adelsberg BR, Parham DM, Siegal M, Cunningham-Rundles S, Armstrong D: Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. N Engl J Med 305:1439–1444, 1981

    Google Scholar 

  134. Badger AM, Bernard DB, Idelson BA, Cooperband SR: Depressed spontaneous cellular cytotoxicity associated with normal or enhanced antibody dependent cellular cytotoxicity in patients on chronic haemodialysis. Clin Exp Immunol 45:568–575, 1981

    Google Scholar 

  135. Lang I, Taraba I, Petrany G: Deceased antibody-dependent and spontaneous cell-mediated cytotoxicity in patients with chronic renal failure. Immunol Lett 3:267–271, 1981

    Google Scholar 

  136. Karsh J, Dorval G, Osterland CK: Natural cytotoxicity in rheumatoid arthritis and systemic lupus erythematosus. Clin Immunol Immunopathol 19:437–446, 1981

    Google Scholar 

  137. Silverman SL, Cathcart ES: Natural killing in systemic lupus erythematosus: Inhibitory effects of serum. Clin Immunol Immunopathol 17:219–226, 1980

    Google Scholar 

  138. Seybold D, Ryan EA, Wall JR: Natural cytotoxicity of blood mononuclear cells from normal subjects and patients with Hashimoto's Thyroiditis against normal thyroid cells. J Clin Lab Immunol 6:241–244, 1981

    Google Scholar 

  139. Benczur M, Petrani GG, Palffy G, Varga M, Talas M, Kotsy I, Foldes I, Hollan S: Dysfunction of natural killer cells in multiple sclerosis, a possible pathogenetic factor. Clin Exp Immunol 39:657–662, 1980

    Google Scholar 

  140. Santoli D, Hall W, Kastrukoff L, Lisak RP, Perussia B, Trinchieri G, Koprowski H: Cytotoxic activity and interferon production by lymphocytes from patients with multiple sclerosis. J Immunol 126:1274–1278, 1981

    Google Scholar 

  141. Silver RM, Rederman D, Zvaifler NJ, Naides S: Studies of rheumatoid synovial fluid lymphocytes. I. Evidence for activated natural killer (NK) like cells. J Immunol 128:1758–1763, 1982

    Google Scholar 

  142. Blomgren H, Baral E, Edsmyr F, Strender L-E, Petrini B, Wasserman J: Natural killer activity in peripheral lymphocyte population following local radiation therapy. Acta Radiol Oncol 19:139–143, 1980

    Google Scholar 

  143. Guillou PJ, Hegarty J, Ramsden C, Davison AM, Will EJ, Giles GR: Changes in human natural killer activity early and late after renal transplantation using conventional immunosuppression. Transplantation 33:414–423, 1982

    Google Scholar 

  144. Kalland T, Haukaas S: Effect of treatment with diethylstilbestrol polyestradiol phosphate or estramustine phosphate (Estracyt) on natural killer cell activity in patients with prostatic cancer. Invest Urol 18:437–439, 1981

    Google Scholar 

  145. Koren HS, Anderson SJ, Fischer DG, Copeland CS, Jensen PJ: Regulation of human natural killing. J Immunol 127:2007–2013, 1981

    Google Scholar 

  146. Targan SR: The dual interaction of prostaglandin E2 (PGE2) and interferon (IFN) on NK lytic activation: Enhanced capacity of effector target lytic interactions (recycling) and blockage of pre-NK cell recruitment. J Immunol 127:1424–1428, 1981

    Google Scholar 

  147. Bankhurst AD: The modulation of human natural killer cell activity by prostaglandins. J Clin Lab Immunol 7:85–91, 1982

    Google Scholar 

  148. Hersey P, Edwards A, Lewis R, Kemp A, McInnes J: Deficient natural killer cell activity in a patient with Fanconi's anemic and squamous cell carcinoma: Association with a defect in interferon release. Clin Exp Immunol 48:205–212, 1982

    Google Scholar 

  149. Uchida A, Micksche M: Suppressor cells for natural killer activity in carcinomatous pleural effusions of cancer patients. Cancer Immunol Immunother 11:255–263, 1981

    Google Scholar 

  150. Allavena P, Introna M, Mangioni C, Mantovani A: Inhibition of natural killer activity by tumor-associated lymphoid cells from ascites ovarian carcinomas. J Natl Cancer Inst 67:319–325, 1981

    Google Scholar 

  151. Eremin O, Coombs RRA, Ashby J: Lymphocytes infiltrating human breast cancers lack K-cell activity and show low levels of NK-cell activity. Br J Cancer 44:166–176, 1981

    Google Scholar 

  152. Leung DYM, Parkman R, Feller J, Wood N, Geha RS: Cell-mediated cytotoxicity against skin fibroblasts in atopic dermatitis. J Immunol 128:1736–1741, 1982

    Google Scholar 

  153. Kakumu S, Hara T, Goji H, Sakamoto N: Lymphocyte cytotoxicity against Chang liver cells in chronic active hepatitis. Cell Immunol 36:46–53, 1978

    Google Scholar 

  154. Dienstag JL, Bhan AK: Enhancedin vitro cell-mediated cytotoxicity in chronic hepatitis B virus infection: Absence of specificity for virus expressed antigen on target cell membranes. J Immunol 125:2269–2275, 1980

    Google Scholar 

  155. Dokhelar MC, Wiels J, Lipinski M, Tetaud C, Devergie A, Gluckman E, Tursz T: Natural killer cell activity in human bone marrow recipients. Early appearance of peripheral natural killer activity in graft-versus host disease. Transplantation 31:61–65, 1981

    Google Scholar 

  156. Lopez C, Kirkpatrick D, Sorell M, O'Reilly RJ, Ching C: Association between pre-transplant natural kill and graft-versus-host disease after stem-cell transplantation. Lancet 2:1103–1107, 1979

    Google Scholar 

  157. Ennis FA, Meager A, Beare AS, Yi-Hua Q, Riley D, Schwarz G, Schild GC, Rook AH: Interferon induction and increased natural killer-cell activity in influenza infections in man. Lancet 1:891–893, 1981

    Google Scholar 

  158. Ojo-Amaize EA, Salimonu LS, Williams AIO, Akinwolere OAO, Shabo R, Alm SG, Wigzell H: Positive correlation between degree of parasitemia, interferon titers, and natural killer cell activity in plasmodium falciparum-infected children. J Immunol 127:2296–2300, 1981

    Google Scholar 

  159. Roder JC, Haliotis T: Do NK cells play a role in anti-tumor surveillance. Immunol Today 1:96–100, 1980

    Google Scholar 

  160. Kiessling R, Wigzell H: An analysis of the murine NK cell as to structure, function and biological relevance. Immunol Rev 44:165–208, 1979

    Google Scholar 

  161. Karre K, Klein GO, Kiessling R, Klein G, Roder JC: Low naturalin vivo resistance to syngeneic leukemias in natural killer deficient mice. Nature 284:624–626, 1980

    Google Scholar 

  162. Talmadge JE, Meyers KM, Prieur DJ, Starkey SR: Role of natural killer cells in tumor growth and metastasis in beige mice. Nature 284:622–644, 1980

    Google Scholar 

  163. Salomon JC, Goldberg NC, Lynch NR: Cancer induction by methylcholanthrene and metastatic spread of transplantable tumors in Chediak-Higashi (beige) mice. Cancer Immunol Immunother 7:67–71, 1980

    Google Scholar 

  164. Gorczinski RM: Evidence forin vivo protection against murine sarcoma virus-induced tumors by T lymphocytes from immune animals. J Immunol 112:533–539, 1974

    Google Scholar 

  165. Haliotis T, Roder JC, Dexter D: Evidence forin vivo NK reactivity against primary tumors.In Natural Killer Cells, RB Herberman (ed). New York, Academic Press (in press), 1982, Vol 2

    Google Scholar 

  166. Argov S, Cochran AJ, Karre K, Klein GO, Klein G: Incidence and type of tumors induced in C57B1 bg/bg mice and +/bg littermates by oral administration of DMBA. Int J Cancer 28:739–746, 1981

    Google Scholar 

  167. Lamm KM, Linna TJ: Protection of newly hatched chickens from Marek's disease (JMV) by normal spleen cells from older animals.In Advances in Comparative Leukemia Research, P Bentvelzen (ed). Amsterdam, Elsevier/North-Holland, 1977

    Google Scholar 

  168. Collins JL, Patek PO, Cohn M: Tumorigenicity and lysis by natural killers. J Exp Med 153:89–106, 1981

    Google Scholar 

  169. Lavrovsky VA, Viksler VK: Immunological properties of malignant and nonmalignant sublines of L-cells. Cancer Res 40:3252–3258, 1980

    Google Scholar 

  170. Hanna N, Fidler IJ: Relationship between metastatic potential and resistance to natural killer cell-mediated cytotoxicity in three murine tumor systems. J Natl Cancer Inst 66:1183–1190, 1981

    Google Scholar 

  171. Hanna N, Burton RC: Definitive evidence that natural killer (NK) cells inhibit experimental tumor metastasisin vivo. J Immunol 127:1754–1758, 1981

    Google Scholar 

  172. Dent PB, Fish LA, White JF, Good RA: Chediak-Higashi syndrome. Observations on the nature of the associated malignancy. Lab Invest 15:1634–1642, 1966

    Google Scholar 

  173. Heidenreich W, Jagla K, Schussler J, Borner P, Dehnhard F, Kalden JR, Leibold W, Peter HH, Deicher H: Spontaneous cell-mediate cytotoxicity (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) in peripheral blood and draining lymph nodes of patients with mammary carcinoma. Cancer Immunol Immunother 7:65–69, 1979

    Google Scholar 

  174. Werkmeister JA, Pihl E, Nind AAP, Flannery GR, Nairn RC: Immunoreactivity by intrinsic lymphoid cells in colorectal carcinoma. Br J Cancer 40:839–847, 1979

    Google Scholar 

  175. Vose BM, Moore M: Natural cytotoxicity in humans: Susceptibility of freshly isolated tumor cells to lysis. J Natl Cancer Inst 65:257–263, 1980

    Google Scholar 

  176. Vose BM, Vanky F, Argov S, Klein E: Natural cytotoxicity in man: Activity of lymph node and tumor infiltrating lymphocytes. Eur J Immunol 7:753–757, 1977

    Google Scholar 

  177. Vose BM, Gallagher P, Moore M, Schofield PF: Specific and non-specific lymphocyte cytotoxicity in colon carcinoma. Br J Cancer 44:846–855, 1981

    Google Scholar 

  178. Moore M, Vose BM: Extravascular natural cytotoxicity in man: Anti-K562 activity of lymph node and tumour infiltrating lymphocytes. Int J Cancer 27:265–272, 1981

    Google Scholar 

  179. Vanky FT, Argov SA, Einhorn SA, Klein E: Role of alloantigens in natural killing. Allogeneic but not autologous tumor biopsy cells are sensitive for interferon-induced cytotoxicity of human blood lymphocytes. J Exp Med 151:1151–1165, 1980

    Google Scholar 

  180. Poste G, Fidler IJ: The pathogenesis of cancer metastasis. Nature 283:139–146, 1980

    Google Scholar 

  181. Gorelik E, Feldman M, Segal S: Selection of 3LL tumor subline resistant to natural effector cells concomitantly selected for increased metastatic potency. Cancer Immunol Immunother 12:105–109, 1982

    Google Scholar 

  182. Brooks CG, Flannery GR, Willmott N, Austin EB, Kenwrick S, Baldwin RW: Tumour cells in metastatic deposits with altered sensitivity to natural killer cells. Int J Cancer 28:191–198, 1981

    Google Scholar 

  183. Mukherji B, Dayal Y: Lymphocyte cytotoxicity of patients developing multiple primary melanomas. Cancer 46:1566–1571, 1980

    Google Scholar 

  184. Morales A, Ersil A: Prophylaxis of recurrent bladder cancer with bacillus Calmette-Guerin.In Cancer of the genitourinary tract, DE Johnson, ML Samuels (eds). New York, Raven Press, 1979, pp 121–132

    Google Scholar 

  185. Lamm DL, Thor DE, Harris SC, Reyna JA, Stogdill VD, Radwin HM: Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer. J Urol 124:38–42, 1980

    Google Scholar 

  186. Saal JG, Riethmuller G, Eiber EP, Hadam M, Ehinger H, Schneider W: Regional BCG therapy of malignant melanoma:In vitro monitoring of spontaneous cytolytic activity of circulating lymphocytes. Cancer Immunol Immunother 3:27–33, 1977

    Google Scholar 

  187. Einhorn S, Blomgren H, Strander H: Interferon and spontaneous cytotoxicity in man. II. Studies in patients receiving exogenous leukocyte interferon. Acta Med Scand 204:477–482, 1978

    Google Scholar 

  188. Huddlestone JR, Merigan TC, Oldstone MBA: Induction and kinetics of natural killer cells in humans following interferon therapy. Nature 282:417–419, 1979

    Google Scholar 

  189. Goldfarb RH, Herberman RB: Characteristics of natural killer cells and possible mechanisms for their cytotoxic activity. Adv Inflam Res 4:45–72, 1982

    Google Scholar 

  190. Wakasugi H, Oshimi K, Miyata M, Morioka Y: Augmentation of natural killer (NK) cell activity by a streptococcal preparation, OK-432, in patients with malignant tumors. J Clin Immunol 1:154–162, 1981

    Google Scholar 

  191. Ortaldo JR, Oldham RK, Cannon GC, Herberman RB: Specificity of natural cytotoxic reactivity of normal lymphocytes against a myeloid cell line. J Natl Cancer Inst 59:77–82, 1977

    Google Scholar 

  192. Gorelik E, Herberman RB: Susceptibility of various strains of mice to urethan-induced lung tumors and depressed natural killer cell activity. J Natl Cancer Inst 67:1317–1322, 1981

    Google Scholar 

  193. Keller R, Aguet M, Tovey M, Stitz L: Prevention of interferon-induced augmentation of cellular antitumor effector mechanisms by phorbol esters. Cancer Res 42:1468–1472, 1982

    Google Scholar 

  194. Minato N, Bloom BR, Jones C, Holland J, Reid LM: Mechanism of rejection of virus-persistently infected tumor cells by athymic nude mice. J Exp Med 149:1117–1133, 1979

    Google Scholar 

  195. Santoli D, Trinchieri G, Leif FS: Cell-mediated cytotoxicity against virus-infected target cells in human. I. Characterization of effector lymphocytes. J Immunol 121:526–531, 1978

    Google Scholar 

  196. Harfast B, Andersson T, Perlmann P: Immunoglobulin independent natural cytotoxicity of Fc receptor bearing human blood lymphocytes to mumps virus infected target cells. J Immunol 121:755–761, 1978

    Google Scholar 

  197. Shellam GR, Allan JE, Papadimitriou JM, Bancroft GJ: Increased susceptibility to cytomegalovirus infection in beige mutant mice. Proc Natl Acad Sci USA 78:5104–5108, 1981

    Google Scholar 

  198. Blazer B, Patarroyo M, Klein E, Klein G: Increased sensitivity of human lymphoid lines to natural killer cells after induction of the Epstein-Barr viral cycle by superinfection on sodium butyrate. J Exp Med 151:614–621, 1980

    Google Scholar 

  199. Bon-van Norloos AA, Pegels HG, van Oers RHJ, Silberbush J, Feltkamp-Vroom TM, Goudsmit R, Zeijlemaker WP, von dem Borne AEG, Melief CJM: Proliferation of Tγ cells with killer-cell activity in two patients with neutropenia and recurrent infections. N Engl J Med 302:933–937, 1980

    Google Scholar 

  200. Ferrarini M, Romagnani S, Montesoro E, Zicca A, Del Prete GF, Nocera A, Maggi E, Leprini A, Grossi CE: A lymphoproliferative disorder of the large granular lymphocytes with a natural killer activity. J Clin Immunol (in press), 1982

  201. Pross HF, Pater J, Dwosh I, Giles A, Gallinger LA, Rubin P, Corbett WEN, Galbraith P, Baines MG: Studies of human natural killer cells. III. Neutropenia associated with unusual characteristics of antibody dependent and natural killer cell-mediated cytotoxicity. J Clin Immunol 2:126–134, 1981

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Microbiology & Immunology, Queen's University, K7L 3N6, Kingston, Ontario, Canada

    John C. Roder & Hugh F. Pross

  2. Department of Radiation Oncology, Queen's University, K7L 3N6, Kingston, Ontario, Canada

    Hugh F. Pross

Authors
  1. John C. Roder
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hugh F. Pross
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Roder, J.C., Pross, H.F. The biology of the human natural killer cell. J Clin Immunol 2, 249–263 (1982). https://doi.org/10.1007/BF00915064

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00915064

Key words

Search

Navigation