Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1983 Jun;80(12):3782–3786. doi: 10.1073/pnas.80.12.3782

Macrophage activation: priming activity from a T-cell hybridoma is attributable to interferon-gamma.

J L Pace, S W Russell, R D Schreiber, A Altman, D H Katz
PMCID: PMC394136  PMID: 6407020

Abstract

Antiviral and macrophage-priming activities in the supernatant medium of a subclone of a concanavalin A-stimulated mouse T-cell hybridoma were investigated. The two activities were associated with a molecular weight of approximately 50,000 and could not be separated by various approaches. Both activities were eliminated by a highly specific neutralizing antibody against mouse interferon-gamma, but not by antibody against interferon-alpha and -beta. The ratio of priming to antiviral activity in the hybridoma culture supernate was indistinguishable from the ratio obtained with mouse interferon-gamma prepared by recombinant DNA technology. It was concluded from these data that the priming activity in hybridoma culture supernates was attributable to interferon-gamma and that this mediator is one form of the lymphokine macrophage-activating factor. Interferon-gamma was greater than 800 times more efficient at priming mouse macrophages for tumor cell killing than was a mixture of interferon-alpha and -beta. This finding contributes to growing awareness that type II interferon may have greater immunoregulatory potential than type I interferons.

Full text

PDF
3782

Selected References

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

  1. Altman A., Sferruzza A., Weiner R. G., Katz D. H. Constitutive and mitogen-induced production of T cell growth factor by stable T cell hybridoma lines. J Immunol. 1982 Mar;128(3):1365–1371. [PubMed] [Google Scholar]
  2. Blalock J. E., Georgiades J. A., Langford M. P., Johnson H. M. Purified human immune interferon has more potent anticellular activity than fibroblast or leukocyte interferon. Cell Immunol. 1980 Feb;49(2):390–394. doi: 10.1016/0008-8749(80)90041-6. [DOI] [PubMed] [Google Scholar]
  3. Blalock J. E., Gifford G. E. Inhibition of interferon action by vitamin A. J Gen Virol. 1975 Dec;29(3):315–324. doi: 10.1099/0022-1317-29-3-315. [DOI] [PubMed] [Google Scholar]
  4. Boraschi D., Tagliabue A. Interferon-induced enhancement of macrophage-mediated tumor cytolysis and its difference from activation by lymphokines. Eur J Immunol. 1981 Feb;11(2):110–114. doi: 10.1002/eji.1830110209. [DOI] [PubMed] [Google Scholar]
  5. Claeys H., Van Damme J., De Ley M., Vermylen C., Billiau A. Activation of natural cytotoxicity of human peripheral blood mononuclear cells by interferon: a kinetic study and comparison of different interferon types. Br J Haematol. 1982 Jan;50(1):85–94. doi: 10.1111/j.1365-2141.1982.tb01893.x. [DOI] [PubMed] [Google Scholar]
  6. Erickson K. L., Cicurel L., Gruys E., Fidler I. J. Murine T-cell hybridomas that produce lymphokine with macrophage-activating factor activity as a constitutive product. Cell Immunol. 1982 Sep 1;72(1):195–201. doi: 10.1016/0008-8749(82)90297-0. [DOI] [PubMed] [Google Scholar]
  7. Gray P. W., Leung D. W., Pennica D., Yelverton E., Najarian R., Simonsen C. C., Derynck R., Sherwood P. J., Wallace D. M., Berger S. L. Expression of human immune interferon cDNA in E. coli and monkey cells. Nature. 1982 Feb 11;295(5849):503–508. doi: 10.1038/295503a0. [DOI] [PubMed] [Google Scholar]
  8. Hibbs J. B., Jr, Taintor R. R., Chapman H. A., Jr, Weinberg J. B. Macrophage tumor killing: influence of the local environment. Science. 1977 Jul 15;197(4300):279–282. doi: 10.1126/science.327547. [DOI] [PubMed] [Google Scholar]
  9. Katz D. H., Bechtold T. E., Altman A. Construction of T cell hybridomas secreting allogeneic effect factor. J Exp Med. 1980 Oct 1;152(4):956–968. doi: 10.1084/jem.152.4.956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kelso A., Glasebrook A. L., Kanagawa O., Brunner K. T. Production of macrophage-activating factor by T lymphocyte clones and correlation with other lymphokine activities. J Immunol. 1982 Aug;129(2):550–556. [PubMed] [Google Scholar]
  11. Kleinschmidt W. J., Schultz R. M. Similarities of murine gamma interferon and the lymphokine that renders macrophages cytotoxic. J Interferon Res. 1982;2(2):291–299. doi: 10.1089/jir.1982.2.291. [DOI] [PubMed] [Google Scholar]
  12. Kniep E. M., Domzig W., Lohmann-Matthes M. L., Kickhöfen B. Partial purification and chemical characterization of macrophage cytotoxicity factor (MCF, MAF) and its separation from migration inhibitory factor (MIF). J Immunol. 1981 Aug;127(2):417–422. [PubMed] [Google Scholar]
  13. Levin J., Tomasulo P. A., Oser R. S. Detection of endotoxin in human blood and demonstration of an inhibitor. J Lab Clin Med. 1970 Jun;75(6):903–911. [PubMed] [Google Scholar]
  14. Meltzer M. S., Benjamin W. R., Farrar J. J. Macrophage activation for tumor cytotoxicity: induction of macrophage tumoricidal activity by lymphokines from EL-4, a continuous T cell line. J Immunol. 1982 Dec;129(6):2802–2807. [PubMed] [Google Scholar]
  15. Morrison D. C., Leive L. Fractions of lipopolysaccharide from Escherichia coli O111:B4 prepared by two extraction procedures. J Biol Chem. 1975 Apr 25;250(8):2911–2919. [PubMed] [Google Scholar]
  16. Osborne L. C., Georgiades J. A., Johnson H. M. Classification of interferons with antibody to immune interferon. Cell Immunol. 1980 Jul 15;53(1):65–70. doi: 10.1016/0008-8749(80)90426-8. [DOI] [PubMed] [Google Scholar]
  17. Osborne L. C., Georgiades J. A., Johnson H. M. Large-scale production and partial purification of mouse immune interferon. Infect Immun. 1979 Jan;23(1):80–86. doi: 10.1128/iai.23.1.80-86.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pace J. L., Russell S. W. Activation of mouse macrophages for tumor cell killing. I. Quantitative analysis of interactions between lymphokine and lipopolysaccharide. J Immunol. 1981 May;126(5):1863–1867. [PubMed] [Google Scholar]
  19. Ratliff T. L., Thomasson D. L., McCool R. E., Catalona W. J. T-cell hybridoma production of macrophage activation factor (MAF) I. Separation of MAF from interferon gamma. J Reticuloendothel Soc. 1982 May;31(5):393–397. [PubMed] [Google Scholar]
  20. Roberts W. K., Vasil A. Evidence for the identity of murine gamma interferon and macrophage activating factor. J Interferon Res. 1982;2(4):519–532. doi: 10.1089/jir.1982.2.519. [DOI] [PubMed] [Google Scholar]
  21. Ruco L. P., Meltzer M. S. Macrophage activation for tumor cytotoxicity: development of macrophage cytotoxic activity requires completion of a sequence of short-lived intermediary reactions. J Immunol. 1978 Nov;121(5):2035–2042. [PubMed] [Google Scholar]
  22. Schreiber R. D., Altman A., Katz D. H. Identification of a T cell hybridoma that produces large quantities of macrophage-activating factor. J Exp Med. 1982 Sep 1;156(3):677–689. doi: 10.1084/jem.156.3.677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schultz R. M., Chirigos M. A. Similarities among factors that render macrophages tumoricidal in lymphokine and interferon preparations. Cancer Res. 1978 Apr;38(4):1003–1007. [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Sonnenfeld G., Meruelo D., McDevitt H. O., Merigan T. C. Effect of type I and type II interferons on murine thymocyte surface antigen expression: induction or selection? Cell Immunol. 1981 Jan 15;57(2):427–439. doi: 10.1016/0008-8749(81)90101-5. [DOI] [PubMed] [Google Scholar]
  27. Taramelli D., Holden H. T., Varesio L. Endotoxin requirement for macrophage activation by lymphokines in a rapid microcytotoxicity assay. J Immunol Methods. 1980;37(3-4):225–232. doi: 10.1016/0022-1759(80)90309-9. [DOI] [PubMed] [Google Scholar]
  28. Virelizier J. L., Chan E. L., Allison A. C. Immunosuppressive effects of lymphocyte (type II) and leucocyte (type I) interferon on primary antibody responses in vivo and in vitro. Clin Exp Immunol. 1977 Nov;30(2):299–304. [PMC free article] [PubMed] [Google Scholar]
  29. Wallach D., Fellous M., Revel M. Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature. 1982 Oct 28;299(5886):833–836. doi: 10.1038/299833a0. [DOI] [PubMed] [Google Scholar]
  30. Weinberg J. B., Hibbs J. B., Jr In vitro modulation of macrophage tumoricidal activity: partial characterization of a macrophage-activating factor(s) in supernatants of NaIO4-treated peritoneal cells. J Reticuloendothel Soc. 1979 Sep;26(3):283–293. [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES