Abstract
Natural killer (NK) cells are a class of lymphocytes important in immune resistance to viral and other serious diseases. The cytotoxic function, or ‘killing activity’ of NK cells has become important in studies of the effects of stress and other psychosocial factors on physical health. Unfortunately, research on NK cell function has been plagued by discrepancies in the methods of interpreting NK cytotoxicity data. We briefly review some of the variations in measuring NK cell activity and present a new model for interpreting these results, introducing maximal target cell lysis (A) and the slope of the cytolytic curve (k) as parameters that attempt to make full use of the information and the statistical power in NK cell cytotoxicity data. Examples of these interpretation methods are presented using NK cytotoxicity data from a group of metastatic breast cancer patients. This approach will be useful in applications of NK cell measurement in psychoneuroimmunology research. Copyright © 2006 John Wiley & Sons, Ltd.
Keywords: natural killer, cytotoxicity, psychoneuroimmunology, cancer
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REFERENCES
- Baron RS, Cutrona CE, Hicklin D, Russell DW, Lubaroff DM. Social support and immune function among spouses of cancer patients. J Pers Soc Psychol 1990; 59(2): 344–52. [DOI] [PubMed] [Google Scholar]
- Biron CA, Nguyen KB, Pien GC, Cousens LP, Salazar‐Mather TP. Natural killer cells in antiviral defense: function and regulation by innate cytokines. Annu Rev Immunol 1999; 17: 189–220. [DOI] [PubMed] [Google Scholar]
- Bryant J, Day R, Whiteside TL, Herberman RB. Calculation of lytic units for the expression of cell‐mediated cytotoxicity. J Immunol Methods 1992; 146(1): 91–103. [DOI] [PubMed] [Google Scholar]
- Buske‐Kirschbaum A, Kirschbaum C, Stierle H, Lehnert H, Hellhammer D. Conditioned increase of natural killer cell activity (NKCA) in humans. Psychosom Med 1992; 54(2): 123–32. [DOI] [PubMed] [Google Scholar]
- Cerottini J, Engers H, Macdonald H, Brunner T. Generation of cytotoxic T lymphocytes in vitro. I. Response of normal and immune mouse spleen cells in mixed leukocyte cultures. J Exp Med 1974; 140(3): 703–17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cheknev SB. Measurement of NK cells' cytotoxicity and IFN production as square of the area under the functional curve. Russ J Immunol 2002; 7(2): 123–8. [PubMed] [Google Scholar]
- Clark D, Phillips R, Miller R. Characterization of cells that suppress the cytotoxic activity of T lymphocytes. I. Quantitative measurement of inhibitor cells. J Immunol Methods 1976; 116(4): 1020–9. [PubMed] [Google Scholar]
- Dhabhar FS, Miller AH, McEwen BS, Spencer RL. Effects of stress on immune cell distribution. Dynamics and hormonal mechanisms. J Immunol 1995; 154(10): 5511–27. [PubMed] [Google Scholar]
- Esterling B, Antoni M, Fletcher M, Margulies S, Schneiderman N. Emotional disclosure through writing or speaking modulates latent Epstein‐Barr virus antibody titers. J Consult Clin Psychol 1994; 62(1): 130–40. [DOI] [PubMed] [Google Scholar]
- Friberg D, Bryant J, Whiteside T. Measurement of natural killer (NK) activity and NK‐cell quantification. Methods: A Companion to Methods in Enzymology, 1996; 9: 316–26. [DOI] [PubMed] [Google Scholar]
- Gan X, Zhang L, Solomon GF, Bonavida B. Mechanism of norepinephrine‐mediated inhibition of human NK cytotoxic functions: inhibition of cytokine secretion, target binding, and programming for cytotoxicity. Brain Behav Immun 2002; 16(3): 227–46. [DOI] [PubMed] [Google Scholar]
- Godoy‐Ramirez K, Franck K, Gaines H. A novel method for the simultaneous assessment of natural killer cell conjugate formation and cytotoxicity at the single‐cell level by multi‐parameter flow cytometry. J Immunol Methods 2000. 239(1–2): 35–44. [DOI] [PubMed] [Google Scholar]
- Hatam L, Schuval S, Bonagura V. Flow cytometric analysis of natural killer cell function as a clinical assay. Cytometry 1994; 16: 59–68. [DOI] [PubMed] [Google Scholar]
- Herbert T, Cohen S. Stress and immunity in humans: a meta‐analytic review. Psychosomatic Medicine 1993; 55: 364–79. [DOI] [PubMed] [Google Scholar]
- Irwin M, Daniels M, Smith T, Bloom E, Weiner H. Impaired natural killer cell activity during bereavement. Brain Behav Immun, 1987; 1(1): 98–104. [DOI] [PubMed] [Google Scholar]
- Kiecolt‐Glaser J, Garner W, Speicher C, Penn G, Holliday J, Glaser R. Psychosocial modifiers of immunocompetence in medical students. Psychosom Med 1984; 46(1): 7–14. [DOI] [PubMed] [Google Scholar]
- Landmann R, Muller F, Perini C, Wesp M, Erne P, Buhler F. Changes of immunoregulatory cells induced by psychological and physical stress: relationship to plasma catecholamines. Clin Exp Immunol 1984; 58(1): 127–35. [PMC free article] [PubMed] [Google Scholar]
- Levy SM, Herberman RB, Maluish AM, Schlien B, Lippman M. Prognostic risk assessment in primary breast cancer by behavioral and immunological parameters. Health Psychol 1985; 4: 99–113. [DOI] [PubMed] [Google Scholar]
- Li J, Zhang Z, Jin B, Tian F. Natural killer cell cytotoxicity assay with time‐resolved fluorimetry. Sci China C Life Sci 1996; 39(2): 217–24. [PubMed] [Google Scholar]
- Maes M, Meltzer H, Stevens W, Calabrese J, Cosyns P. Natural killer cell activity in major depression: relation to circulating natural killer cells, cellular indices of the immune response, and depressive phenomenology. Prog Neuropsychopharmacol Biol Psychiatry 1994; 18(4): 717–30. [DOI] [PubMed] [Google Scholar]
- Moretta L, Bottino C, Pende D, Mingari MC, Biassoni R, Moretta A. Human natural killer cells: their origin, receptors and function. Eur J Immunol 2002; 32(5): 1205–11. [DOI] [PubMed] [Google Scholar]
- Naliboff B, Benton D, Solomon G, Morley J. Immunological changes in young and old adults during brief laboratory stress. Psychosom Med 1991; 53: 121–32. [DOI] [PubMed] [Google Scholar]
- Pacifici R, Di Carlo S, Bacosi A, Altieri I, Pichini S, Zuccaro P. Modified procedure for labelling target cells in a europium release assay of natural killer cell activity. J Immunol Methods 1993; 161(1): 135–7. [DOI] [PubMed] [Google Scholar]
- Pollock R, Zimmerman S, Fuchshuber P, Lotzova E. Lytic units reconsidered: pitfalls in calculation and usage. J Clin Lab Anal 1991; 4(4): 274–82. [DOI] [PubMed] [Google Scholar]
- Pross H, Baines M, Rubin P, Shragge P, Patterson M. Spontaneous human lymphocyte‐mediated cytotoxicity against tumour target cells. IX. The quantitation of natural killer cell activity. J Clin Immunol 1981; 1(1): 51–63. [DOI] [PubMed] [Google Scholar]
- Provinciali M, Di Stefano G, Fabris N. Optimization of cytotoxic assay by target cell retention of the fluorescent dye carboxyfluoescein diacetate (CFDA) and comparison with conventional 51Cr release assay. Journal of Immunological Methods 1992; 155: 19–24. [DOI] [PubMed] [Google Scholar]
- Racz T, Sacks P, Van V, Taylor D, Young G, Bugis S, Savage H, Schantz S. The analysis of natural killer cell activity by flow cytometry. Arch Otolaryngol Head Neck Surg 1990; 116(4): 440–6. [DOI] [PubMed] [Google Scholar]
- Radloff L. The CES‐D Scale: A Self‐Report Depression Scale for Research in the General Population. Applied Psychological Measurement 1977; 1(3): 385–401. [Google Scholar]
- Schedlowski M, Jacobs R, Stratmann G, Richter S, Hadicke A, Tewes U, Wagner T, Schmidt R. Changes of natural killer cells during acute psychological stress. J Clin Immunol 1993; 13(2): 119–26. [DOI] [PubMed] [Google Scholar]
- Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, Takeda K, Dommelen SL, Degli‐Esposti MA, Hayakawa Y. Activation of NK cell cytotoxicity. Mol Immunol 2005; 42(4): 501–10. [DOI] [PubMed] [Google Scholar]
- Spiegel D, Sephton SE. Psychoneuroimmune and endocrine pathways in cancer: effects of stress and support. Semin Clin Neuropsychiatry 2001; 6(4): 252–65. [DOI] [PubMed] [Google Scholar]
- Trinchieri G. Biology of natural killer cells. Adv Immunol 1989; 47: 187–376. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whiteside T, Bryant J, Day R, Herberman R. Natural killer cytotoxicity in the diagnosis of immune dysfunction: criteria for a reproducible assay. J Clin Lab Anal, 1990; 4(2): 102–14. [DOI] [PubMed] [Google Scholar]
- Whiteside T, Herberman R. The role of natural killer cells in human disease. Clin Immunol Immunopathol 1989; 53(1): 1–23. [DOI] [PubMed] [Google Scholar]
- Whiteside T, Herberman R. Role of human natural killer cells in health and disease. Clin Diagn Lab Immunol 1994; 1(2): 125–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Whiteside T, Herberman R. The role of natural killer cells in immune surveillance of cancer. Curr Opin Immunol 1995; 7(5): 704–10. [DOI] [PubMed] [Google Scholar]
- Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res 2003; 90: 127–156. [DOI] [PubMed] [Google Scholar]
