Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1978 Jun 1;147(6):1621–1636. doi: 10.1084/jem.147.6.1621

In vitro induction of cytotoxic effector cells with spontaneous killer cell specificity

PMCID: PMC2184326  PMID: 308088

Abstract

The present work shows that stimulation of peripheral blood lymphocytes with autologous or allogeneic B-cell lines leads to a strong induction of cytotoxic effector cells with spontaneous killer (SK) cell specificity, apart from the specific response directed against the particular stimulating cell. To demonstrate this we have determined a relative target cell specificity in the SK system, defined by the short- term 51Cr release assay, and established a relative specificity index (RSI). Using this approach we have been able to show that killer cells induced during a 5-day cocultivation period with B-cell lines have a similar PSI to that of unstimulated SK cells. In addition, we have shown that such killer cells can be induced from several different lymphocyte subpopulations and that they, in contrast to SK cells, do not express Fc receptors. The implications of these findings in relation to the nature, mechanism, and biological significance of the SK cell system is discussed.

Full Text

The Full Text of this article is available as a PDF (1,015.6 KB).

Selected References

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

  1. Akira D., Takasugi M. Loss of specific natural cell-mediated cytotoxicity with absorption of natural antibodies from serum. Int J Cancer. 1977 Jun 15;19(6):747–755. doi: 10.1002/ijc.2910190603. [DOI] [PubMed] [Google Scholar]
  2. Billing R., Rafizadeh B., Drew I., Hartman G., Gale R., Terasaki P. Human B-lymphocyte antigens expressed by lymphocytic and myelocytic leukemia cells. I. Detection by rabbit antisera. J Exp Med. 1976 Jul 1;144(1):167–178. doi: 10.1084/jem.144.1.167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Epstein M. A., Achong B. G., Barr Y. M., Zajac B., Henle G., Henle W. Morphological and virological investigations on cultured Burkitt tumor lymphoblasts (strain Raji). J Natl Cancer Inst. 1966 Oct;37(4):547–559. [PubMed] [Google Scholar]
  4. Hinuma Y., Grace J. T., Jr Cloning of immunoglobulin-producing human leukemic and lymphoma cells in long-term cultures. Proc Soc Exp Biol Med. 1967 Jan;124(1):107–111. doi: 10.3181/00379727-124-31677. [DOI] [PubMed] [Google Scholar]
  5. Jondal M. Surface markers on human B and T lymphocytes. IV. Distribution of surface markers on resting and blast-transformed lymphocytes. Scand J Immunol. 1974;3(6):739–747. doi: 10.1111/j.1365-3083.1974.tb01309.x. [DOI] [PubMed] [Google Scholar]
  6. Jondal M. Surface markers on human B and T lymphocytes. V. Characterization of the lymphoproliferative response to three different lectins and allogeneic lymphocytes by surface markers. Scand J Immunol. 1974;3(6):749–755. doi: 10.1111/j.1365-3083.1974.tb01310.x. [DOI] [PubMed] [Google Scholar]
  7. Kaplan J., Shope T. C., Peterson W. D., Jr Epstein-barr virus-negative human malignant T-cell lines. J Exp Med. 1974 May 1;139(5):1070–1076. doi: 10.1084/jem.139.5.1070. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kiessling R., Petranyi G., Kärre K., Jondal M., Tracey D., Wigzell H. Killer cells: a functional comparison between natural, immune T-cell and antibody-dependent in vitro systems. J Exp Med. 1976 Apr 1;143(4):772–780. doi: 10.1084/jem.143.4.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Klein G., Lindahl T., Jondal M., Leibold W., Menézes J., Nilsson K., Sundström C. Continuous lymphoid cell lines with characteristics of B cells (bone-marrow-derived), lacking the Epstein-Barr virus genome and derived from three human lymphomas. Proc Natl Acad Sci U S A. 1974 Aug;71(8):3283–3286. doi: 10.1073/pnas.71.8.3283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Koide Y., Takasugi M. Determination of specificity in natural cell-mediated cytotoxicity by natural antibodies. J Natl Cancer Inst. 1977 Oct;59(4):1099–1105. doi: 10.1093/jnci/59.4.1099. [DOI] [PubMed] [Google Scholar]
  11. Kuntz M. M., Innes J. B., Weksler M. E. Lymphocyte transformation induced by autologous cells. IV. Human T-lymphocyte proliferation induced by autologous or allogeneic non-T lymphocytes. J Exp Med. 1976 May 1;143(5):1042–1054. doi: 10.1084/jem.143.5.1042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ling N. R., Steel C. M., Wallin J., Hardy D. A. The interaction of normal lymphocytes and cells from lymphoid cell lines (LCL). V. Cytotoxic properties of activated lymphocytes. Immunology. 1974 Feb;26(2):345–358. [PMC free article] [PubMed] [Google Scholar]
  13. Lozzio C. B., Lozzio B. B. Cytotoxicity of a factor isolated from human spleen. J Natl Cancer Inst. 1973 Feb;50(2):535–538. doi: 10.1093/jnci/50.2.535. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Opelz G., Kiuchi M., Takasugi M., Terasaki P. I. Autologous stimulation of human lymphocyte subpopulation. J Exp Med. 1975 Nov 1;142(5):1327–1333. doi: 10.1084/jem.142.5.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Peter H. H., Pavie-Fischer J., Fridman W. H., Aubert C., Cesarini J. P., Roubin R., Kourilsky F. M. Cell-mediate cytotoxicity in vitro of human lymphocytes against a tissue culture melanoma cell line (igr3). J Immunol. 1975 Aug;115(2):539–548. [PubMed] [Google Scholar]
  17. Pross H. F., Baines M. G., Jondal M. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. II. Is the complement receptor necessarily present on the killer cells? Int J Cancer. 1977 Sep 15;20(3):353–358. doi: 10.1002/ijc.2910200306. [DOI] [PubMed] [Google Scholar]
  18. Royston I., Graze P. R., Pitts R. B. Failure of cultured human T-cell lymphoid lines to stimulate in mixed leukocyte culture. J Natl Cancer Inst. 1974 Aug;53(2):361–367. doi: 10.1093/jnci/53.2.361. [DOI] [PubMed] [Google Scholar]
  19. Svedmyr E. A., Deinhardt F., Klein G. Sensitivity of different target cells to the killing action of peripheral lymphocytes stimulated by autologous lymphoblastoid cell lines. Int J Cancer. 1974 Jun 15;13(6):891–903. doi: 10.1002/ijc.2910130617. [DOI] [PubMed] [Google Scholar]
  20. Svedmyr E., Jondal M., Leibold W. Stimulation of normal lymphocytes with autologous lymphoid cell lines: properties of derived killer cells. Scand J Immunol. 1975;4(7):721–734. doi: 10.1111/j.1365-3083.1975.tb02680.x. [DOI] [PubMed] [Google Scholar]
  21. Svedmyr E. Long-term maintenance in vitro of human T cells by repeated exposure to the same stimulator cells. Differences when using repeated stimulation in allogeneic mixed leukocyte culture and when using stimulation with autologous lymphoblastoid cells. Scand J Immunol. 1975 Sep;4(5-6):421–427. doi: 10.1111/j.1365-3083.1975.tb02647.x. [DOI] [PubMed] [Google Scholar]
  22. Svedmyr E., Wigzell H., Jondal M. Sensitization of human lymphocytes against autologous or allogeneic lymphoblastoid cell lines: characteristics of the reactive cells. Scand J Immunol. 1974;3(4):499–508. doi: 10.1111/j.1365-3083.1974.tb01283.x. [DOI] [PubMed] [Google Scholar]
  23. Vande Stouwe R. A., Kunkel H. G., Halper J. P., Weksler M. E. Autologous mixed lymphocyte culture reactions and generation of cytotoxic T cells. J Exp Med. 1977 Dec 1;146(6):1809–1814. doi: 10.1084/jem.146.6.1809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wernet P. Human Ia-type alloantigens: methods of detection, aspects of chemistry and biology, markers for disease states. Transplant Rev. 1976;30:271–298. doi: 10.1111/j.1600-065x.1976.tb00223.x. [DOI] [PubMed] [Google Scholar]
  25. West W. H., Cannon G. B., Kay H. D., Bonnard G. D., Herberman R. B. Natural cytotoxic reactivity of human lymphocytes against a myeloid cell line: characterization of effector cells. J Immunol. 1977 Jan;118(1):355–361. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES