Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1990 May;70(1):116–120.

Indirect inhibition of generation of murine lymphokine-activated killer cell activity in splenocyte cultures by interferon-gamma.

T Y Chao 1, H Ohnishi 1, T M Chu 1
PMCID: PMC1384091  PMID: 2113034

Abstract

The effect of mouse recombinant interferon-gamma (rIFN-gamma) on murine lymphokine-activated killer (LAK) cell activity was investigated using natural killer (NK)-resistant, spontaneously developed, weakly immunogenic and highly tumourigenic, syngeneic murine mammary adenocarcinoma, JC, mimicking that of human disease, as the target. Murine YAC-1 also was used as a target cell line. rIFN-gamma, when used in combination with recombinant interleukin-2 (rIL-2), was shown to exhibit a suppressed effect on LAK cell activity generated from BALB/c mouse splenocytes, compared to that with rIL-2 alone. The decrease in LAK cell activity was rIFN-gamma dose-dependent. Kinetic study revealed that this inhibitory effect was demonstrated only when rIFN-gamma was added to the medium at the early phase of rIL-2 culture. The inhibitory effect on LAK cell generation by rIFN-gamma was completely abrogated when the nylon-wool-treated non-adherent 'macrophage-free' splenocytes were incubated with rIL-2 and rIFN-gamma. These results indicated that the LAK cell activity generated from murine splenocytes cultured with rIL-2 could be depressed by rIFN-gamma, and that the macrophages may be involved as mediators.

Full text

PDF
116

Selected References

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

  1. Boraschi D., Censini S., Bartalini M., Tagliabue A. Regulation of arachidonic acid metabolism in macrophages by immune and nonimmune interferons. J Immunol. 1985 Jul;135(1):502–505. [PubMed] [Google Scholar]
  2. Capone P. M., Kadohama N., Chu T. M. Immunotherapy in a spontaneously developed murine mammary carcinoma with syngeneic monoclonal antibody. Cancer Immunol Immunother. 1987;25(2):93–99. doi: 10.1007/BF00199947. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chao T. Y., Chu T. M. Characterization of a new spontaneously developed murine mammary adenocarcinoma in syngeneic BALB/c hosts. In Vitro Cell Dev Biol. 1989 Jul;25(7):621–626. doi: 10.1007/BF02623632. [DOI] [PubMed] [Google Scholar]
  4. Chao T. Y., Ohnishi H., Chu T. M. Augmentation of murine lymphokine (rIL-2)-activated killer cell activity by indomethacin. Mol Biother. 1989;1(6):318–322. [PubMed] [Google Scholar]
  5. Chouaib S., Welte K., Mertelsmann R., Dupont B. Prostaglandin E2 acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down-regulation of transferrin receptor expression. J Immunol. 1985 Aug;135(2):1172–1179. [PubMed] [Google Scholar]
  6. ElMasry M. N., Fox E. J., Rich R. R. Sequential effects of prostaglandins and interferon-gamma on differentiation of CD8+ suppressor cells. J Immunol. 1987 Aug 1;139(3):688–694. [PubMed] [Google Scholar]
  7. Giovarelli M., Santoni A., Jemma C., Musso T., Giuffrida A. M., Cavallo G., Landolfo S., Forni G. Obligatory role of IFN-gamma in induction of lymphokine-activated and T lymphocyte killer activity, but not in boosting of natural cytotoxicity. J Immunol. 1988 Oct 15;141(8):2831–2836. [PubMed] [Google Scholar]
  8. Hoyer M., Meineke T., Lewis W., Zwilling B., Rinehart J. Characterization and modulation of human lymphokine (interleukin 2) activated killer cell induction. Cancer Res. 1986 Jun;46(6):2834–2838. [PubMed] [Google Scholar]
  9. Ibayashi Y., Hoon D. S., Golub S. H. The regulatory effect of adherent cells on lymphokine activated killer cells. Cell Immunol. 1987 Dec;110(2):365–378. doi: 10.1016/0008-8749(87)90129-8. [DOI] [PubMed] [Google Scholar]
  10. Itoh K., Shiiba K., Shimizu Y., Suzuki R., Kumagai K. Generation of activated killer (AK) cells by recombinant interleukin 2 (rIL 2) in collaboration with interferon-gamma (IFN-gamma). J Immunol. 1985 May;134(5):3124–3129. [PubMed] [Google Scholar]
  11. Johnston R. B., Jr Current concepts: immunology. Monocytes and macrophages. N Engl J Med. 1988 Mar 24;318(12):747–752. doi: 10.1056/NEJM198803243181205. [DOI] [PubMed] [Google Scholar]
  12. Kalland T., Belfrage H., Bhiladvala P., Hedlund G. Analysis of the murine lymphokine-activated killer (LAK) cell phenomenon: dissection of effectors and progenitors into NK- and T-like cells. J Immunol. 1987 Jun 1;138(11):3640–3645. [PubMed] [Google Scholar]
  13. Lala P. K., Parhar R. S. Cure of B16F10 melanoma lung metastasis in mice by chronic indomethacin therapy combined with repeated rounds of interleukin 2: characteristics of killer cells generated in situ. Cancer Res. 1988 Mar 1;48(5):1072–1079. [PubMed] [Google Scholar]
  14. Mazumder A., Rosenberg S. A. Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2. J Exp Med. 1984 Feb 1;159(2):495–507. doi: 10.1084/jem.159.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ortaldo J. R. Regulation of natural killer activity. Cancer Metastasis Rev. 1987;6(4):637–651. doi: 10.1007/BF00047471. [DOI] [PubMed] [Google Scholar]
  16. Ottow R. T., Steller E. P., Sugarbaker P. H., Wesley R. A., Rosenberg S. A. Immunotherapy of intraperitoneal cancer with interleukin 2 and lymphokine-activated killer cells reduces tumor load and prolongs survival in murine models. Cell Immunol. 1987 Feb;104(2):366–376. doi: 10.1016/0008-8749(87)90038-4. [DOI] [PubMed] [Google Scholar]
  17. Pross H. F., Baines M. G., Rubin P., Shragge P., Patterson M. S. Spontaneous human lymphocyte-mediated cytotoxicity against tumor target cells. IX. The quantitation of natural killer cell activity. J Clin Immunol. 1981 Jan;1(1):51–63. doi: 10.1007/BF00915477. [DOI] [PubMed] [Google Scholar]
  18. Ramsdell F. J., Golub S. H. Generation of lymphokine-activated killer cell activity from human thymocytes. J Immunol. 1987 Sep 1;139(5):1446–1453. [PubMed] [Google Scholar]
  19. Rosenstein M., Yron I., Kaufmann Y., Rosenberg S. A. Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2. Cancer Res. 1984 May;44(5):1946–1953. [PubMed] [Google Scholar]
  20. Sayers T. J., Mason A. T., Ortaldo J. R. Regulation of human natural killer cell activity by interferon-gamma: lack of a role in interleukin 2-mediated augmentation. J Immunol. 1986 Mar 15;136(6):2176–2180. [PubMed] [Google Scholar]
  21. Silvennoinen O., Vakkila J., Hurme M. Accessory cells, dendritic cells, or monocytes, are required for the lymphokine-activated killer cell induction from resting T cell but not from natural killer cell precursors. J Immunol. 1988 Aug 15;141(4):1404–1409. [PubMed] [Google Scholar]
  22. Suzuki R., Handa K., Itoh K., Kumagai K. Natural killer (NK) cells as a responder to interleukin 2 (IL 2). I. Proliferative response and establishment of cloned cells. J Immunol. 1983 Feb;130(2):981–987. [PubMed] [Google Scholar]
  23. Svedersky L. P., Shepard H. M., Spencer S. A., Shalaby M. R., Palladino M. A. Augmentation of human natural cell-mediated cytotoxicity by recombinant human interleukin 2. J Immunol. 1984 Aug;133(2):714–718. [PubMed] [Google Scholar]
  24. Takai N., Tanaka R., Yoshida S., Hara N., Saito T. In vivo and in vitro effect of adoptive immunotherapy of experimental murine brain tumors using lymphokine-activated killer cells. Cancer Res. 1988 Apr 15;48(8):2047–2052. [PubMed] [Google Scholar]
  25. Vujanovic N. L., Herberman R. B., Hiserodt J. C. Lymphokine-activated killer cells in rats: analysis of tissue and strain distribution, ontogeny, and target specificity. Cancer Res. 1988 Feb 15;48(4):878–883. [PubMed] [Google Scholar]
  26. Wang A., Lu S. D., Mark D. F. Site-specific mutagenesis of the human interleukin-2 gene: structure-function analysis of the cysteine residues. Science. 1984 Jun 29;224(4656):1431–1433. doi: 10.1126/science.6427925. [DOI] [PubMed] [Google Scholar]
  27. Yang J. C., Mulé J. J., Rosenberg S. A. Murine lymphokine-activated killer (LAK) cells: phenotypic characterization of the precursor and effector cells. J Immunol. 1986 Jul 15;137(2):715–722. [PubMed] [Google Scholar]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES