Advertisement

Molecular Mechanism of Natural Killer Cell-Mediated Cytotoxicity

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

Abstract

Cytotoxic effector systems mediated by cells and humoral factors have been discovered and appear to play an important role in the host defense mechanism against infection and newly arising neoplasia. Several cytotoxic effector cells have been characterized, all of which have in common the ability to interact with and destroy unwanted target cells. However, the underlying molecular mechanism by which the cytotoxic cell destroys the target is not yet completely resolved. Several potential mechanisms have been proposed for cell mediated cytotoxicity (CMC), such as the necessity of cell to cell contact resulting in membrane perturbation, transfer of cytotoxic materials from the effector to the target, co-factors present on target cells that facilitate lysis, pore formation, etc. It is possible that all of these mechanisms may participate in a particular cytolytic reaction and different mechanisms may operate with different cytotoxic effector cells.

Keywords

Natural Killer Target Cell Effector Cell Cell Mediate Cytotoxicity Acquire Immune Deficiency Syndrome Patient 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    B. Bonavida, T. P. Bradley, J. Fan, J. Hiserodt, R. Effros, and H. Wexler. Molecular interactions in T cell-mediated cytotoxicity. Immunol. Rev. 72:119, (1983).CrossRefGoogle Scholar
  2. 2.
    B. Bonavida, T. P. Bradley, and E. A. Grimm. The single cell assay in cell-mediated cytotoxicity. Immunol. Today 4:196, (1983).CrossRefGoogle Scholar
  3. 3.
    S. Targan, E. Grimm, and B. Bonavida. A single cell marker or active NK cytotoxicity: Only a fraction of target binding lymphocytes on killer cells. J. Clin. Immunol. 4:165, (1980).Google Scholar
  4. 4.
    J. C. Roder, A. Rosen, E. M. Fenyo, and F. A. Troy. Target-effector interaction in the natural killer cell system: Isolation of target structures. Proc. Natl. Acad. Sci. USA 76:1405. (1979).ADSCrossRefGoogle Scholar
  5. 5.
    J. A. Werkmeister, S. A. Helfand, T. Haliotis, H. Pross, and J. C. Roder. Specificity of natural killer (NK) cells: Nature of target cell structures. In NK Cells and Other Natural Effector Cells, RB Herverman (ed.) New York, Academic Press (1982).Google Scholar
  6. 6.
    R. B. Herberman. NK cells and other Natural Effector Cells. New York, Academic Press, (1982).Google Scholar
  7. 7.
    T. P. Bradley, and B. Bonavida. Mechanism 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 cells as determined by the single cell conjugate assay. J. Immunol. 129:2260, (1982).Google Scholar
  8. 8.
    S. C. Wright, and B. Bonavida. Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity. IV. Interferon-induced inhibition of NK target cell susceptibility is due to a defect in their ability to stimulate release of natural killer cytotoxic factors (NKCF). J. Immunol. 130:2965, (1983).Google Scholar
  9. 9.
    J. Safrit, S. C. Wright, and B. Bonavida. Mechanism of defective NK activity following irradiation with ultraviolet light. (submitted for publication).Google Scholar
  10. 10.
    B. Bonavida, J. Kiatz, and M. Gottlieb. Mechanism of defective NK cell activity in acquired immune deficiency syndrome (AIDS). I. Defective trigger on NK cells for NKCF production by target cells and restoration by IL-2. J. Immunol. 137:1157, (1986).Google Scholar
  11. 11.
    M. L. Weitzen, and B. Bonavida. Mechanism of inhibition of human natural killer activity by ultraviolet radiation. J. Immunol. 133:3128, (1984).Google Scholar
  12. 12.
    S. C. Wright, and B. Bonavida. Studies on the mechanism of natural killer cytotoxicity. I. Release of cytotoxic factors specific for NK sensitive target cells (NKCF) selectively cytotoxic to NK-sensitive target cells. J. Immunol. 130:2960, (1982).Google Scholar
  13. 13.
    S. C. Wright, M. L. Weitzen, R. Kahle, G. A. Granger, and B. Bonavida. Studies on the mechanism of natural killer cytotoxicity. I. Coculture of human PBL with NK-sensitive or resistant cell lines stimulates release of natural killer cytotoxic factors (NKCF) selectively cytotoxic to NK-sensitive target cells. J. Immunol. 130:2479, (1983).Google Scholar
  14. 14.
    G. Trincheri, and D. Santoli. Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells: Enhancement of human natural killer cells activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J. Exp. Med. 147:1314, (1978).CrossRefGoogle Scholar
  15. 15.
    S. C. Graves, J. Bramhall, S. C. Wright, and B. Bonavida. Studies on the mechanism of natural killer cell-mediated cytotoxicity. IX. Induction of release of natural killer cell cytotoxic factors (NKCF) from human peripheral blood lymphocytes by a phorbol ester and ionophores suggest a role for protein kinase C activation. (submitted for publication).Google Scholar
  16. 16.
    G. Trinchieri, D. Santoli, R. R. Dee, and B. B. Knowles. Antiviral activity induced by culturing lymphocytes with tumor-derived versus transformed cells. Enhancement of human natural killer cell activity by interferon, and antagonistic inhibition of susceptibility of target cells to lysis. J. Exp. Med. 147:1314, (1978).CrossRefGoogle Scholar
  17. 17.
    A. Silva, B. Bonavida, and S. Targan. Mode of action of interferon-mediated modulation of natural killer cytotoxic activity: recruitment of pre-NK cells and enhanced kinetics of lysis. J. Immunol. 125:479, (1980).Google Scholar
  18. 18.
    S. C. Wright, and B. Bonavida. Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity. III. Interferon-pretreatment of effector cell augments the lytic activity of natural killer cytotoxic factors (NKCF). J. Immunol. 130:2960, (1983).Google Scholar
  19. 19.
    R. H. Goldfarb, T. T. Timonen, and R. B. Herberman. The role of neutral serum proteases in the mechanism of tumor cell lysis by human natural killer cells. In NK Cells and Other Natural Effector Cells, RB Herberman (ed.) New York, Academic Press (1982) p 931.CrossRefGoogle Scholar
  20. 20.
    D. Hudig, D. Redelman, and L. Minning. Evidence for proteases with specificity of cleavage at aromatic amino acids in human natural cell-mediated cytotoxicity. In NK Cells and Other Natural Effector Cells, RB Herberman (ed). New York, Academic Press (1982) p 923.CrossRefGoogle Scholar
  21. 21.
    S. C. Wright, and B. Bonavida. Evidence for the involvement of proteolytic enzymes in the production of natural killer cytotoxic factors. In Natural Killer Activity and Its Regulation, T Hoshino et al. (eds.) Amsterdam, Excerpta Medica (1984) p 145.Google Scholar
  22. 22.
    S. C. Wright, and B. Bonavida. YAC-1 variant clones selected for resistance to natural killer cytotoxic factors are also resistant to natural killer cell-mediated cytotoxicity. Proc. Natl. Acad. Sci. USA 80:1688, (1983).ADSCrossRefGoogle Scholar
  23. 23.
    S. C. Wright, K. Kane, W. R. Clark, and B. Bonavida. Studies on the mechanism of natural killer cell-mediated cytotoxicity. VIII. Evidence for the involvement of target cell papain-sensitive binding sites for natural killer cytotoxic factors in NK CMC reactions. (submitted for publication).Google Scholar
  24. 24.
    S. C. Wright, and B. Bonavida. Studies on the mechanism of natural killer cell-mediated cytotoxicity. X. Evidence for the role of NKCF in the NK lytic mechanism: U-937 variants resistant to TNF- are still NK sensitive in CMC reactions whereas variants resistant to NKCF are NK resistant. (submitted).Google Scholar
  25. 25.
    S. C. Wrigth, J. C. Roder, J. Werkmeister, and B. Bonavida. Studies on the mechanism of natural killer (NK) cell-mediated cytotoxicity. VI. The NK resistant YAC-6–28 variant binds NK cells and stimulates release of natural killer cytotoxic factors (NKCF) but is not susceptible of lysis by NKCF. (submitted for publication).Google Scholar
  26. 26.
    R. C. Roozemond, P. Van der Geer, and B. Bonavida. Effect of altered membrane structure on NK cell mediated cytotoxicity II. Conversion of NK-resistant tumor cells into NK sensitive targets upon fusion with liposomes containing NK-sensitive membranes. J. Immunol. (In press).Google Scholar
  27. 27.
    R. C. Roozemond, D. C. Urli, S. C. Wright, S. C. Graves and S. C. Bonavida. Lysis of natural killer-resistant tumor cells by liposome-encapsulated natural killer cytotoxic factors (NKCF) as a proof that cell surface receptors for NKCF are not functionally involved in the actual killing process (submitted for publication).Google Scholar
  28. 28.
    S. C. Wright, S. M. Wilbur, and B. Bonavida. Studies on the mechanism of natural killer cell-mediated cytotoxicity. VI. Characterization of human, rat, and murine natural killer cytotoxic factors. Natl. Immun. Cell Growth Resul. 4:202, (1985).Google Scholar
  29. 29.
    G. A. Granger, S. L. Orr and R. S. Yamamoto. Lymphotoxins, macrophage cytotoxins, and tumor necrosis factors: An interrelated family of antitumor effector molecules. J. Clin. Immunol. 5:217, (1985)CrossRefGoogle Scholar
  30. 30.
    M. L. Weitzen, R. S. Yamamoto, and G. A. Granger. Identification of human lymphocyte derived lymphotoxins with binding and cell lytic activity on NK-sensitive cell lines in vitro. Cell. Immunol. 77:30, (1983).CrossRefGoogle Scholar
  31. 31.
    P. Gray, B. Aggarwal, C. Benton, T. Bringman, W. Henzel, J. Jarrett, D. Leung, B. Moffat, P. Ng, L. Sevedersky, M. Palladino, and G. Nedwin. Cloning and expression of the cDNA for human lymphotoxins: A lymphokine with tumor necrosis factor. Nature 312:721. (1984).ADSCrossRefGoogle Scholar
  32. 32.
    S. C. Wright, and BH. Bonavida. Studies on the mechanism of natural killer cell-mediated cytotoxicity. IX. Functional comparison of human natural killer cytotoxic factors with recombinant lymphotoxin and tumor necrosis factor. (submitted).Google Scholar
  33. 33.
    E. Carswell, L. Old, R. Kassel, S. Green, N. Fiore, and B. Williamson. An endotoxin-induced serum factor that causes necrosis of tumors. Proc. Natl. Acad. Sci. USA 72:3666. (1985).ADSCrossRefGoogle Scholar
  34. 34.
    D. Pennica, G. E. Nedwin, J. S. Hayflick, P. H. Seeburg, R. Deryuck, M. A. Palladino, W. J. Kohr, B. B. Aggarwal, and D. V. Goddel. Human tumor necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature 312:724, (1984).ADSCrossRefGoogle Scholar
  35. 35.
    P. J. Millard, M. A. Henkart, C. W. Reynolds, and P. A. Henkart. Purification and properties of cytoplasmic granules from cytotoxic rat LGL tumors. J. Immunol. 123:3197, (1984).Google Scholar
  36. 36.
    E. R. Podak, and G. Dennert. Assembly of two types of tubules with putative cytolytic function in cloned natural killer cells. Nature 302:442, (1983).ADSCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Benjamin Bonavida
    • 1
  1. 1.Department of Microbiology and Immunology, UCLA School of MedicineUniversity of California at Los AngelesLos AngelesUSA

Personalised recommendations