Antibody-Mediated Cytotoxicity

  • James W. Kazura


Contact of an Fc receptor (FcR)-bearing effector cell and a potential biologic target may occur in the presence of antibodies directed against the surface of the target. When this interaction culminates in damage or killing of the biologic target, it is referred to as antibody-dependent cell-mediated cytotoxicity (ADCC). A multitude of studies indicate that ADCC reactions are involved in immune functions which may be beneficial or deleterious to the whole animal. For example, allograft and tumor rejection, viral resistance (Cerottini and Brunner, 1974; Kohl et al., 1977), and host defense against multicellular helminths (Ellner and Mahmoud, 1982) are in large part effected by ADCC reactions. On the other hand, life-threatening disease states such as immune thrombocytopenic purpura and immune hemolytic anemia also involve ADCC reactions (Kurlander et al., 1978).


Natural Killing Effector Cell Immune Thrombocytopenic Purpura Schistosoma Mansoni ADCC Activity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Anderson, C. L., and Spiegelberg, H. L., 1981, Macrophage receptors for IgE: Binding of IgE to specific IgE Fc receptors on a human macrophage cell line, U937, J. Immunol. 126: 2470.PubMedGoogle Scholar
  2. Andersson, B., Skogland, A.-C., Ronnholm, M., Lindsten, T., Lamon, E. W., Collison, E. W., and Wahia, A. S., 1981, Functional aspects of IgM and IgG Fc receptors on murine T-lymphocytes, Immunol. Rev. 56: 21.CrossRefGoogle Scholar
  3. Babior, B. M., 1978, Oxygen-dependent microbial killing of phagocytes, N. Engl. J. Med. 298: 659.PubMedCrossRefGoogle Scholar
  4. Bass, D. A., and Szejda, P., 1979, Mechanisms of killing of newborn larvae of Trichinella spiralis by neutrophil and eosinophil leukocytes: Killing by generators of hydrogen peroxide in vitro, J. Clin. Invest. 65: 1558.CrossRefGoogle Scholar
  5. Borregaard, N., and Kragballe, K., 1982, The oxygen-dependent cell-mediated cytotoxicity of human monocytes and neutrophils, Adv. Exp. Med. Biol. 141: 71.PubMedCrossRefGoogle Scholar
  6. Bradley, T. P., and Bonavida, B., 1982, Mechanisms of cell-mediated cytotoxicity at the single cell level. IV. Natural killing and antibody-dependent cellular cytotoxicity can be mediated by the same human effector cell as determined by the two-target conjugate assay, J. Immunol. 129: 2260.PubMedGoogle Scholar
  7. Brier, A. M., Chess, L., and Schlossman, S. F., 1975, Human antibody-dependent cellular cytotoxicity, J. Clin. Invest. 56: 1580.PubMedCrossRefGoogle Scholar
  8. Butterworth, A. E., Sturrock, R. F., Houba, V., Mahmoud, A. A. F., Sher, A., and Rees, P. H., 1975, Eosinophils as mediators of antibody-dependent damage to schistosomula, Nature (London) 256: 727.CrossRefGoogle Scholar
  9. Butterworth, A. E., Wassom, D. L., Gleich, G. J., Loegering, D. A., and David, J. R., 1979, Damage to schistosomula of Schistosoma mansoni induced directly by eosinophil major basic protein, J. Immunol. 122: 221.PubMedGoogle Scholar
  10. Capron, M., Capron, A., Dessaint, J.-P., Torpier, G., Johanson, S. G. O., and Prin, L., 1981, Fc receptors for IgE on human and rat eosinophils, J. Immunol. 126: 2087.PubMedGoogle Scholar
  11. Capron, M., Spiegelberg, H. L., Prin, L., Bennich, H., Butterworth, A. E., Pierce, R. J., Ouassi, M. A., and Capron, A., 1984, Role of IgE receptors in effector function of human eosinophils, J. Immunol. 132: 462.PubMedGoogle Scholar
  12. Cerottini, J. C., and Brunner, K. T., 1974, Cell-mediated cytotoxicity, allograft rejection and tumor immunity, Adv. Immunol. 18: 67.PubMedCrossRefGoogle Scholar
  13. Clark, R. A., and Klebanoff, S. J., 1977, Studies on the mechanism of antibody-dependent poly-morphonuclear leukocyte-mediated cytotoxicity, J. Immunol. 119: 1413.PubMedGoogle Scholar
  14. Conkling, P., Klassen, D. K., and Sagone, A. L., Jr., 1982, Comparison of antibody-dependent cytotoxicity mediated by human polymorphonuclear cells, monocytes, and alveolar macrophages, Blood 60: 1290.PubMedGoogle Scholar
  15. Dourmashkin, R. R., Deteix, D., Simone, C. B., and Henkart, P., 1980, Electron microscopic demonstration of lesions in target cell membranes associated with antibody-dependent cellular cytotoxicity, Clin. Exp. Immunol. 42: 554.Google Scholar
  16. Ellner, J. J., and Mahmoud, A. A. F., 1982, Phagocytes and worms: David and Goliath, revisited, Rev. Infect. Dis. 4: 698.PubMedCrossRefGoogle Scholar
  17. Fanger, M. W., Shen, L., Pugh, J., and Bernier, G. M., 1980, Subpopulations of human peripheral granulocytes and monocytes express receptors for IgA, Proc. Natl. Acad. Sci. USA 77: 3640.PubMedCrossRefGoogle Scholar
  18. Fleer, A., Roos, P., van den Borne, A. E. G., and Engelfrist, C. P., 1979, Cytotoxic activity of human monocytes towards sensitized red cells is not dependent on the generation of reactive oxygen species, Blood 54: 407.PubMedGoogle Scholar
  19. Garagiola, D. M., Huard, T. K., and LoBuglio, A. F., 1981, Comparison of monocyte and alveolar macrophage antibody-dependent cellular cytotoxicity and Fc-receptor activity, Cell. Immunol. 64: 359.Google Scholar
  20. Greenberg, A. H., and Lydyard, P. M., 1979, Observation of IgGl anti-DNP hybridoma-mediated ADCC and the failure of three IgM anti-DNP hybridomas to mediate ADCC, J. Immunol. 123: 861.PubMedGoogle Scholar
  21. Holm, G., Engvall, E., Hammarstrom, S., and Natvig, J. B., 1974, Antibody-induced hemolytic activity of human blood monocytes, Scand. J. Immunol. 3: 173.Google Scholar
  22. Joseph, M., Capron, A., Butterworth, A. E., Sturrock, R. F., and Houba, V., 1978, Cytotoxicity of human and baboon mononuclear phagocytes against schistosomula in vitro: Induction by immune complexes containing IgE and Schistosoma mansoni antigens, Clin. Exp. Immunol. 33: 48.Google Scholar
  23. Katz, P., Simone, C. B., Henkart, P. A., and Fauci, A. S., 1980, Mechanism of antibody-dependent cellular cytotoxicity, J. Clin. Invest. 65: 55.PubMedCrossRefGoogle Scholar
  24. Kay, H. D., and Horwitz, D. A., 1980, Evidence by reactivity with hybridoma antibodies for a probable myeloid origin of peripheral blood cells active in natural cytotoxicity and antibody-dependent cell-mediated cytotoxicity, J. Clin. Invest. 66: 847.PubMedCrossRefGoogle Scholar
  25. Kazura, J. W., Fanning, M. M., Blumer, J. T., and Mahmoud, A. A. F., 1981, Role of cell-generated H2O2 in granulocyte-mediated killing of schistosomula of Schistosoma mansoni, J. Clin. Invest. 67: 93.PubMedCrossRefGoogle Scholar
  26. Klebanoff, S. J., 1980, Oxygen metabolism and the toxic properties of phagocytes, Ann. Intern. Med. 93: 480.PubMedCrossRefGoogle Scholar
  27. Kohl, S., Starr, S. E., Oleske, J. M., Shore, S. L., Ashman, R. B., and Nakmias, A. J., 1977, Human monocyte-macrophage-mediated antibody-dependent cytotoxicity to herpes simplex virus infected cells, J. Immunol. 118: 729.PubMedGoogle Scholar
  28. Kurlander, R. J., Rosse, W. F., and Logue, G. L., 1978, Quantitative influence of antibody and complement coating of red cells on monocyte-mediated lysis, J. Clin. Invest. 61: 3109.CrossRefGoogle Scholar
  29. Lamon, E. W., Whitten, H. D., Skurzak, H. M., Andersson, B., and Lindin, B., 1975, IgM antibody-dependent cell-mediated cytotoxicity in the Moloney sarcoma virus system: The involvement of T and B lymphocytes as effector cells, J. Immunol. 115: 1288.PubMedGoogle Scholar
  30. Larsson, A., Pisarri-Salsano, S., Ohlander, C., Natvig, J. B., and Perlmann, P., 1975, Destruction of dextran-coated target cells by normal human lymphocytes and monocytes, Scand. J. Immunol. 4: 421.Google Scholar
  31. Leonard, E. J., Ruco, L. P., and Meltzer, M. S., 1978, Characterization of macrophage activation factor, a lymphokine that causes macrophages to become cytotoxic for tumor cells, Cell. Immunol. 41: 347.Google Scholar
  32. Lovchik, J. C., and Hong, R., 1977, Antibody-dependent cell-mediated cytolysis (ADCC): Analyses and projections, Prog. Allergy 22: 1.Google Scholar
  33. Lowell, G. H., Smith, L. F., Griffis, J. M., and Brandt, B. M., 1980a, Antibody-dependent mono-nuclear cell-mediated anti-meningococcal activity, J. Clin. Invest. 66: 260.PubMedCrossRefGoogle Scholar
  34. Lowell, G. H., Smith, L. F., Griffis, J. M., and Brandt, B. M., 1980b, IgA-dependent, monocyte-mediated, antibacterial activity, J. Exp. Med. 152: 452.PubMedCrossRefGoogle Scholar
  35. MacDonald, H. R., Bonnard, G. D., Sordat, B., and Zawodnik, S. A., 1975, Antibody-dependent cell-mediated cytotoxicity: Heterogeneity of effector cells in human peripheral blood, Scand. J. Immunol. 4: 487.Google Scholar
  36. Mayer, M., 1977, Mechanism of cytolysis by lymphocytes: A comparison with complement, J. Immunol. 119: 1195.PubMedGoogle Scholar
  37. Melewicz, F. M., and Spiegelberg, H. L., 1980, Fc receptors for IgE on a subpopulation of human peripheral blood monocytes, J. Immunol. 125: 1026.PubMedGoogle Scholar
  38. Melewicz, F. M., Zeiger, R. S., Mellon, M. H., O’Connor, R. D., and Spiegelberg, H. L., 1981, Increased IgE-dependent cytotoxicity by blood mononuclear cells of allergic patients, Clin. Exp. Immunol. 43: 526.PubMedGoogle Scholar
  39. Nathan, C. F., and Cohn, Z. A., 1980, Role of oxygen-dependent mechanisms in antibody-dependent lysis of tumor cells, J. Exp. Med. 152: 198.PubMedCrossRefGoogle Scholar
  40. Perlmann, H., and Cerottini, J. C., 1979, Cytotoxic lymphocytes, in: The Antigens ( M. Sela, ed.), pp. 173–283, Academic Press, New York.Google Scholar
  41. Pichler, W., Gendelman, F., and Nelson, D., 1979, Fc receptors on human T lymphocytes. II. Cytotoxic capabilities of T gamma, T mu, B, and L cells, Cell. Immunol. 42: 410.Google Scholar
  42. Pincus, S. H., Butterworth, A. E., David, J. R., Robbins, M., and Vadas, M. A., 1981, Antibody-dependent eosinophil-mediated damage to schistosomula of Schistosoma mansoni: Lack of requirement for oxidative metabolism, J. Immunol. 126: 1794.PubMedGoogle Scholar
  43. Quie, P. G., Messner, R. P., and Williams, R. C. Jr., 1968, Phagocytes in subacute bacterial endocarditis. Localization of the primary opsonic site to Fc fragment, J. Exp. Med. 128: 553.PubMedCrossRefGoogle Scholar
  44. Ralph, P., and Nakoinz, I., 1983, Cell-mediated lysis of tumor targets directed by murine monoclonal antibodies of IgM and all IgG isotypes, J. Immunol. 131: 1028.PubMedGoogle Scholar
  45. Ralph, P., Nakoinz, I., Diamond, B., and Yelton, D., 1980, All major classes of murine IgG antibody mediate macrophage phagocytosis and lysis of erythrocytes, J. Immunol. 125: 1885.PubMedGoogle Scholar
  46. Rimm, I. J., Schlossman, S. F., and Reinherz, E. L., 1981, Antibody-dependent cellular cytotoxicity and natural killer-like activity are mediated by subsets of activated T cells, Clin. Immunol. Immunopathol. 21: 134.CrossRefGoogle Scholar
  47. Shaw, G. M., Levy, P. C., and LoBuglio, A. F., 1978, Human monocyte antibody-dependent cell- mediated cytotoxicity to tumor cells, J. Clin. Invest. 62: 1172.PubMedCrossRefGoogle Scholar
  48. Shen, L., and Fanger, M. W., 1981, Secretory IgA antibodies synergize with IgG in promoting ADCC by human polymorphonuclear cells, monocytes, and lymphocytes, Cell. Immunol. 59: 75.Google Scholar
  49. Simone, C. B., 1982, Directed effector cells selectively lyse human tumour cells, Nature (London) 297: 234.CrossRefGoogle Scholar
  50. Simone, C. B., and Henkart, P. A., 1980, Permeability changes induced in erythrocyte ghost targets by antibody-dependent cytotoxic effector cells: Evidence for membrane pores, J. Immunol. 124: 954.PubMedGoogle Scholar
  51. Strober, W., Hague, N. E., Lum, L. G., and Henkart, P. A., 1978, IgA-Fc receptors on mouse lymphoid cells, J. Immunol. 121: 2440.PubMedGoogle Scholar
  52. Tagliabue, A., Nencioni, L., Villa, L., Keren, D. F., Lowell, G. H., and Boraschi, D., 1983, Antibody-dependent cell-mediated anti-bacterial activity of intestinal lymphocytes with secretory IgA, Nature (London) 306: 184.CrossRefGoogle Scholar
  53. Timonen, T., Ortaldo, J. R., and Herberman, R., 1981, Characteristics of human large granular lymphocytes and relationship to natural killer and K cells, J. Exp. Med. 153: 569.PubMedCrossRefGoogle Scholar
  54. Urbaniak, S. J., 1979, ADCC (K-cell) lysis of human erythrocytes sensitized with rhesus alloantibodies: Investigation of in vitro culture variables, Br.J. Haematol. 42: 315.PubMedCrossRefGoogle Scholar
  55. van Furth, R., and Cohn, Z. A., 1968, The origin and kinetics of mononuclear phagocytes, J. Exp. Med. 128: 415.PubMedCrossRefGoogle Scholar
  56. Venge, P., Dahl, R., Hallgre, R., and Olsson, I., 1980, Cationic proteins of human eosinophils and their role in the inflammatory reaction, in: The Eosinophil in Health and Disease ( A. A. F. Mahmoud and K. F. Austen, eds.), pp. 131–142, Grune & Stratton, New York.Google Scholar
  57. Wilson, I., 1972, Studies on the opsonic activity of human secretory IgA using an in vitro phagocytosis system, J. Immunol. 108: 726.PubMedGoogle Scholar
  58. Zarling, J., and Kung, P. C., 1980, Monoclonal antibodies which distinguish between human NK cells and cytotoxic T lymphocytes, Nature (London) 288: 394.CrossRefGoogle Scholar
  59. Zoller, M., Heyman, B., Andrighetto, G., and Wigzell, H., 1982, IgG- and IgM-induced cellular cytotoxicity, Scand. J. Immunol. 16: 379.Google Scholar
  60. Zoller, M., Andrighetto, G. C., Heyman, B., Lamon, E. W., and Wigzell, H., 1983, Characterization of effector cells mediating IgG and IgM antibody-dependent cellular cytotoxicity, Scand. J. Immunol. 17: 19.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • James W. Kazura
    • 1
  1. 1.Division of Geographic Medicine, Department of MedicineCase Western Reserve University and University HospitalsClevelandUSA

Personalised recommendations