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. 1980 Mar;41(3):378–387. doi: 10.1038/bjc.1980.61

Enhancement of human natural cell-mediated cytotoxicity by interferon.

M Moore, M R Potter
PMCID: PMC2010219  PMID: 6155926

Abstract

The effect of exogenous Namalva interferon (IF) on the natural killer (NK) cell activity of human blood lymphocytes was examined against 5 target cell lines (K562, CCRF/CEM, Molt 4, Raji and Bri8) using the 51Cr-release assay. Addition of IF to the test significantly increased the cytotoxicity, though not as much as when effector cells were treated with IF before the test. Augmentation of cytotoxicity was evident after only 1 h pretreatment and was maximal by 6 h. The rate of lysis of susceptible targets by IF-treated effectors markedly exceeded that by their untreated counterparts. Separation of lymphocyte subpopulations (by SRBC-rosette sedimentation and nylon-fibre column filtration) demonstrated that the activities of IF-stimulated and unstimulated cells were similarly distributed, suggesting that the major effect of IF is enhancement of the activity of pre-existing NK cells rather than generation of new populations of effectors. Target cell lines with high and low susceptibility to NK cells showed increased cytotoxicity by IF-treated effector cells. These findings may be relevant to the current discussion of the role of NK cells in immunosurveillance against neoplasia.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Andersson L. C., Nilsson K., Gahmberg C. G. K562--a human erythroleukemic cell line. Int J Cancer. 1979 Feb;23(2):143–147. doi: 10.1002/ijc.2910230202. [DOI] [PubMed] [Google Scholar]
  2. Balkwill F., Watling D., Taylor-Papadimitriou J. Inhibition by lymphoblastoid interferon of growth of cells derived from the human breast. Int J Cancer. 1978 Sep 15;22(3):258–265. doi: 10.1002/ijc.2910220307. [DOI] [PubMed] [Google Scholar]
  3. Braun W., Levy H. B. Interferon preparations as modifiers of immune responses. Proc Soc Exp Biol Med. 1972 Dec;141(3):769–773. doi: 10.3181/00379727-141-36868. [DOI] [PubMed] [Google Scholar]
  4. Djeu J. Y., Heinbaugh J. A., Holden H. T., Herberman R. B. Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol. 1979 Jan;122(1):175–181. [PubMed] [Google Scholar]
  5. Donahoe R. M., Huang K. Y. Interferon preparations enhance phagocytosis in vivo. Infect Immun. 1976 Apr;13(4):1250–1257. doi: 10.1128/iai.13.4.1250-1257.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Einhorn S., Blomgren H., Strander H. Interferon and spontaneous cytotoxicity in man. I. Enhancement of the spontaneous cytotoxicity of peripheral lymphocytes by human leukocyte interferon. Int J Cancer. 1978 Oct 15;22(4):405–412. doi: 10.1002/ijc.2910220407. [DOI] [PubMed] [Google Scholar]
  7. FOLEY G. E., LAZARUS H., FARBER S., UZMAN B. G., BOONE B. A., MCCARTHY R. E. CONTINUOUS CULTURE OF HUMAN LYMPHOBLASTS FROM PERIPHERAL BLOOD OF A CHILD WITH ACUTE LEUKEMIA. Cancer. 1965 Apr;18:522–529. doi: 10.1002/1097-0142(196504)18:4<522::aid-cncr2820180418>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  8. Gisler R. H., Lindahl P., Gresser I. Effects of interferon on antibody synthesis in vitro. J Immunol. 1974 Aug;113(2):438–444. [PubMed] [Google Scholar]
  9. Gresser I. On the varied biologic effects of interferon. Cell Immunol. 1977 Dec;34(2):406–415. doi: 10.1016/0008-8749(77)90262-3. [DOI] [PubMed] [Google Scholar]
  10. Havell E. A., Yip Y. K., Vilcek J. Characteristics of human lymphoblastoid (Namalva) interferon. J Gen Virol. 1978 Jan;38(1):51–59. doi: 10.1099/0022-1317-38-1-51. [DOI] [PubMed] [Google Scholar]
  11. Herberman R. R., Ortaldo J. R., Bonnard G. D. Augmentation by interferon of human natural and antibody-dependent cell-mediated cytotoxicity. Nature. 1979 Jan 18;277(5693):221–223. doi: 10.1038/277221a0. [DOI] [PubMed] [Google Scholar]
  12. Heron I., Berg K., Cantell K. Regulatory effect of interferon on T cells in vitro. J Immunol. 1976 Oct;117(4):1370–1373. [PubMed] [Google Scholar]
  13. Huang K. Y., Donahoe R. M., Gordon F. B., Dressler H. R. Enhancement of phagocytosis by interferon-containing preparations. Infect Immun. 1971 Nov;4(5):581–588. doi: 10.1128/iai.4.5.581-588.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Huber C., Sundström C., Nilsson K., Wigzell H. Surface receptors on human haematopoietic cell lines. Clin Exp Immunol. 1976 Sep;25(3):367–376. [PMC free article] [PubMed] [Google Scholar]
  15. Huddlestone J. R., Merigan T. C., Jr, Oldstone M. B. Induction and kinetics of natural killer cells in humans following interferon therapy. Nature. 1979 Nov 22;282(5737):417–419. doi: 10.1038/282417a0. [DOI] [PubMed] [Google Scholar]
  16. Johnson H. M., Smith B. G., Baron S. Inhibition of the primary in vitro antibody response by interferon preparations. J Immunol. 1975 Jan;114(1 Pt 2):403–409. [PubMed] [Google Scholar]
  17. Jondal M., Targan S. In vitro induction of cytotoxic effector cells with spontaneous killer cell specificity. J Exp Med. 1978 Jun 1;147(6):1621–1636. doi: 10.1084/jem.147.6.1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Koide Y., Takasugi M. Augmentation of human natural cell-mediated cytotoxicity by a soluble factor. I. Production of N-cell-activating factor (NAF). J Immunol. 1978 Sep;121(3):872–879. [PubMed] [Google Scholar]
  19. Lindahl-Magnusson P., Leary P., Gresser I. Interferon inhibits DNA synthesis induced in mouse lymphocyte suspensions by phytohaemagglutinin or by allogeneic cells. Nat New Biol. 1972 May 24;237(73):120–121. doi: 10.1038/newbio237120a0. [DOI] [PubMed] [Google Scholar]
  20. Lindahl P., Leary P., Gresser I. Enhancement by interferon of the specific cytotoxicity of sensitized lymphocytes. Proc Natl Acad Sci U S A. 1972 Mar;69(3):721–725. doi: 10.1073/pnas.69.3.721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Minowada J., Onuma T., Moore G. E. Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J Natl Cancer Inst. 1972 Sep;49(3):891–895. [PubMed] [Google Scholar]
  22. Oehler J. R., Lindsay L. R., Nunn M. E., Holden H. T., Herberman R. B. Natural cell-mediated cytotoxicity in rats. II. In vivo augmentation of NK-cell activity. Int J Cancer. 1978 Feb 15;21(2):210–220. doi: 10.1002/ijc.2910210213. [DOI] [PubMed] [Google Scholar]
  23. Peter H. H., Eife R. F., Kalden J. R. Spontaneous cytotoxicity (SCMC) of normal human lymphocytes against a human melanoma cell line: a phenomenon due to a lymphotoxin-like mediator. J Immunol. 1976 Feb;116(2):342–348. [PubMed] [Google Scholar]
  24. Potter M. R., Moore M. Natural cytotoxic reactivity of human lymphocyte subpopulations. Immunology. 1979 May;37(1):187–194. [PMC free article] [PubMed] [Google Scholar]
  25. Potter M. R., Moore M. PHA stimulation of separated human lymphocyte populations. Clin Exp Immunol. 1975 Sep;21(3):456–467. [PMC free article] [PubMed] [Google Scholar]
  26. Saksela E., Timonen T., Cantell K. Human natural killer cell activity is augmented by interferon via recruitment of 'pre-NK' cells. Scand J Immunol. 1979;10(3):257–266. doi: 10.1111/j.1365-3083.1979.tb01348.x. [DOI] [PubMed] [Google Scholar]
  27. Santoli D., Trinchieri G., Koprowski H. Cell-mediated cytotoxicity against virus-infected target cells in humans. II. Interferon induction and activation of natural killer cells. J Immunol. 1978 Aug;121(2):532–538. [PubMed] [Google Scholar]
  28. Santoli D., Trinchieri G., Lief F. S. Cell-mediated cytotoxicity against virus-infected target cells in humans. I. Characterization of the effector lymphocyte. J Immunol. 1978 Aug;121(2):526–531. [PubMed] [Google Scholar]
  29. Schultz R. M., Papamatheakis J. D., Chirigos M. A. Interferon: an inducer of macrophage activation by polyanions. Science. 1977 Aug 12;197(4304):674–676. doi: 10.1126/science.877584. [DOI] [PubMed] [Google Scholar]
  30. Senik A., Gresser I., Maury C., Gidlund M., Orn A., Wigzell H. Enhancement by interferon of natural killer cell activity in mice. Cell Immunol. 1979 Apr;44(1):186–200. doi: 10.1016/0008-8749(79)90039-x. [DOI] [PubMed] [Google Scholar]
  31. Sonnenfeld G., Mandel A. D., Merigan T. C. The immunosuppressive effect of type II mouse interferon preparations on antibody production. Cell Immunol. 1977 Dec;34(2):193–206. doi: 10.1016/0008-8749(77)90243-x. [DOI] [PubMed] [Google Scholar]
  32. Stewart W. E., 2nd, Gresser I., Tovey M. G., Bandu M., Le Goff S. Identification of the cell multiplication inhibitory factors in interferon preparations as interferons. Nature. 1976 Jul 22;262(5566):300–302. doi: 10.1038/262300a0. [DOI] [PubMed] [Google Scholar]
  33. Strander H., Mogensen K. E., Cantell K. Production of human lymphoblastoid interferon. J Clin Microbiol. 1975 Jan;1(1):116–117. doi: 10.1128/jcm.1.1.116-117.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Trinchieri G., Santoli D. Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis. J Exp Med. 1978 May 1;147(5):1314–1333. doi: 10.1084/jem.147.5.1314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Trinchieri G., Santoli D., Dee R. R., Knowles B. B. Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Identification of the anti-viral activity as interferon and characterization of the human effector lymphocyte subpopulation. J Exp Med. 1978 May 1;147(5):1299–1313. doi: 10.1084/jem.147.5.1299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Trinchieri G., Santoli D., Knowles B. B. Tumour cell lines induce interferon in human lymphocytes. Nature. 1977 Dec 15;270(5638):611–613. doi: 10.1038/270611a0. [DOI] [PubMed] [Google Scholar]
  37. Vignaux F., Gresser I. Differential effects of interferon on the expression of H-2K, H-2D, and Ia antigens on mouse lymphocytes. J Immunol. 1977 Feb;118(2):721–723. [PubMed] [Google Scholar]
  38. Zarling J. M., Sosman J., Eskra L., Borden E. C., Horoszewicz J. S., Carter W. A. Enhancement of T cell cytotoxic responses by purified human fibroblast interferon. J Immunol. 1978 Nov;121(5):2002–2004. [PubMed] [Google Scholar]

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