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. 1978 May 1;147(5):1299–1313. doi: 10.1084/jem.147.5.1299

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

PMCID: PMC2184278  PMID: 650155

Abstract

A viral inhibitor(s) is released in the supernate of mixed cultures containing human or mouse lymphocytes and cells from certain lines. The inhibitor is active against a variety of unrelated viruses and is a protein that is not toxic for cells. It does not inactivate viruses directly, but inhibits viral replication through an intracellular mechanism that involves synthesis by the cells of both RNA and protein. These characteristics identify the inhibitor as an interferon. The anti- viral activity is contained in at least two molecular species, of approximately 25,000 and 45,000 daltons, respectively. In addition to the anti-viral activity, the supernates of the mixed cultures display an anti-cellular activity, the inhibition of DNA synthesis and of cell multiplication. The anti-viral and the anti-cellular activities are positively correlated in supernates from various cultures and in partially purified preparations. The human cell population responsible for interferon production is composed mainly of Fc-receptor positive, surface immunoglobulin negative, non-T-cell lymphocytes. The ability of certain cell lines to induce interferon seems to be preferentially associated with tumor origin or with in vitro transformation by certain viruses (Epstein-Barr virus, murine sarcoma virus).

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Selected References

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  1. 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]
  2. Dahl H., Degre M. Separation of antiviral activity of human interferon from cell growth inhibitory effect. Nature. 1975 Oct 30;257(5529):799–800. doi: 10.1038/257799a0. [DOI] [PubMed] [Google Scholar]
  3. De Maeyer-Guignard J. Mouse leukemia: depression of serum interferon production. Science. 1972 Sep 1;177(4051):797–799. doi: 10.1126/science.177.4051.797. [DOI] [PubMed] [Google Scholar]
  4. Dickler H. B., Kunkel H. G. Interaction of aggregated -globulin with B lymphocytes. J Exp Med. 1972 Jul 1;136(1):191–196. doi: 10.1084/jem.136.1.191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Epstein L. B., Stevens D. A., Merigan T. C. Selective increase in lymphocyte interferon response to vaccinia antigen after revaccination. Proc Natl Acad Sci U S A. 1972 Sep;69(9):2632–2636. doi: 10.1073/pnas.69.9.2632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Evans R., Booth C. G. Inhibition of 125IUdR incorporation by supernatants from macrophage and lymphocyte cultures: a cautionary note. Cell Immunol. 1976 Sep;26(1):120–126. doi: 10.1016/0008-8749(76)90354-3. [DOI] [PubMed] [Google Scholar]
  7. Falcoff R., Oriol R., Iscaki S. Lymphocyte stimulation and interferon induction by 7 S anti-human lymphocyte globulins and their uni- and divalent fragments. Eur J Immunol. 1972 Oct;2(5):476–478. doi: 10.1002/eji.1830020520. [DOI] [PubMed] [Google Scholar]
  8. Falcoff R. Some properties of virus and immune-induced human lymphocyte interferons. J Gen Virol. 1972 Aug;16(2):251–253. doi: 10.1099/0022-1317-16-2-251. [DOI] [PubMed] [Google Scholar]
  9. Gifford G. E., Tibor A., Peavy D. L. Interferon production in mixed lymphocyte cell cultures. Infect Immun. 1971 Jan;3(1):164–166. doi: 10.1128/iai.3.1.164-166.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. 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]
  11. Glasgow L. A. Leukocytes and interferon in the host response to viral infections. II. Enhanced interferon response of leukocytes from immune animals. J Bacteriol. 1966 Jun;91(6):2185–2191. doi: 10.1128/jb.91.6.2185-2191.1966. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Golgher R. R., Paucker K. Blocking of interferon production by chromatographically purified L cell interferon. Proc Soc Exp Biol Med. 1973 Jan;142(1):167–174. doi: 10.3181/00379727-142-36981. [DOI] [PubMed] [Google Scholar]
  13. Graham F. L., Abrahams P. J., Mulder C., Heijneker H. L., Warnaar S. O., De Vries F. A., Fiers W., Van Der Eb A. J. Studies on in vitro transformation by DNA and DNA fragments of human adenoviruses and simian virus 40. Cold Spring Harb Symp Quant Biol. 1975;39(Pt 1):637–650. doi: 10.1101/sqb.1974.039.01.077. [DOI] [PubMed] [Google Scholar]
  14. Green J. A., Cooperband S. R., Kibrick S. Immune specific induction of interferon production in cultures of human blood lymphocytes. Science. 1969 Jun 20;164(3886):1415–1417. doi: 10.1126/science.164.3886.1415. [DOI] [PubMed] [Google Scholar]
  15. Havell E. A., Berman B., Ogburn C. A., Berg K., Paucker K., Vilcek J. Two antigenically distinct species of human interferon. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2185–2187. doi: 10.1073/pnas.72.6.2185. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. 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]
  18. Ida S., Hooks J. J., Siraganian R. P., Notkins A. L. Enhancement of IgE-mediated histamine release from human basophils by viruses: role of interferon. J Exp Med. 1977 Apr 1;145(4):892–906. doi: 10.1084/jem.145.4.892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Julius M. H., Simpson E., Herzenberg L. A. A rapid method for the isolation of functional thymus-derived murine lymphocytes. Eur J Immunol. 1973 Oct;3(10):645–649. doi: 10.1002/eji.1830031011. [DOI] [PubMed] [Google Scholar]
  20. Klein E., Klein G., Nadkarni J. S., Nadkarni J. J., Wigzell H., Clifford P. Surface IgM-kappa specificity on a Burkitt lymphoma cell in vivo and in derived culture lines. Cancer Res. 1968 Jul;28(7):1300–1310. [PubMed] [Google Scholar]
  21. Knight E., Jr Antiviral and cell growth inhibitory activities reside in the same glycoprotein of human fibroblast interferon. Nature. 1976 Jul 22;262(5566):302–303. doi: 10.1038/262302a0. [DOI] [PubMed] [Google Scholar]
  22. Kohn L. D., Friedman R. M., Holmes J. M., Lee G. Use of thyrotropin and cholera toxin to probe the mechanism by which interferon initiates its antiviral activity. Proc Natl Acad Sci U S A. 1976 Oct;73(10):3695–3699. doi: 10.1073/pnas.73.10.3695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kuwata T., Oda T., Sekiya S., Morinaga N. Characteristics of a human cell line successively transformed by Rous sarcoma virus and simian virus 40. J Natl Cancer Inst. 1976 May;56(5):919–926. doi: 10.1093/jnci/56.5.919. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Mahowald M. L., Handwerger B. S., Capertone E. M., Jr, Douglas S. D. A comparative study of procedures for sheep erythrocyte-human-T-lymphocyte rosette formation. J Immunol Methods. 1977;15(3):239–245. doi: 10.1016/0022-1759(77)90061-8. [DOI] [PubMed] [Google Scholar]
  26. Merigan T. C., Finkelstein M. S. Interferon-stimulating and in vivo antiviral effects of various synthetic anionic polymers. Virology. 1968 Jul;35(3):363–374. doi: 10.1016/0042-6822(68)90215-8. [DOI] [PubMed] [Google Scholar]
  27. Mueller J., Brun del Re G., Buerki H., Keller H. U., Hess M. W., Cottier H. Nonspecific acid esterase activity: a criterion for differentiation of T and B lymphocytes in mouse lymph nodes. Eur J Immunol. 1975 Apr;5(4):270–274. doi: 10.1002/eji.1830050411. [DOI] [PubMed] [Google Scholar]
  28. Opitz H. G., Niethammer D., Lemke H., Flad H. D., Huget R. Inhibition of 3H-thymidine incorporation of lymphocytes by a soluble factor from macrophages. Cell Immunol. 1975 Apr;16(2):379–388. doi: 10.1016/0008-8749(75)90126-4. [DOI] [PubMed] [Google Scholar]
  29. Rasheed S., Nelson-Rees W. A., Toth E. M., Arnstein P., Gardner M. B. Characterization of a newly derived human sarcoma cell line (HT-1080). Cancer. 1974 Apr;33(4):1027–1033. doi: 10.1002/1097-0142(197404)33:4<1027::aid-cncr2820330419>3.0.co;2-z. [DOI] [PubMed] [Google Scholar]
  30. Rasmussen L. E., Jordan G. W., Stevens D. A., Merigan T. C. Lymphocyte interferon production and transformation after Herpes simplex infections in humans. J Immunol. 1974 Feb;112(2):728–736. [PubMed] [Google Scholar]
  31. Rhim J. S., Cho H. Y., Huebner R. J. Non-producer human cells induced by murine sarcoma virus. Int J Cancer. 1975 Jan 15;15(1):23–29. doi: 10.1002/ijc.2910150104. [DOI] [PubMed] [Google Scholar]
  32. Santoli D., Trinchieri G., Zmijewski C. M., Koprowski H. HLA-related control of spontaneous and antibody-dependent cell-mediated cytotoxic activity in humans. J Immunol. 1976 Sep;117(3):765–770. [PubMed] [Google Scholar]
  33. Stewart W. E., 2nd, De Clercq E., Billiau A., Desmyter J., De Somer P. Increased susceptibility of cells treated with interferon to the toxicity of polyriboinosinic-polyribocytidylic acid. Proc Natl Acad Sci U S A. 1972 Jul;69(7):1851–1854. doi: 10.1073/pnas.69.7.1851. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Stewart W. E., 2nd, DeClercq E., De Somer P., Berg K., Ogburn C. A., Paucker K. Antiviral and non-antiviral activity of highly purified interferon. Nat New Biol. 1973 Dec 5;246(153):141–143. doi: 10.1038/newbio246141a0. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Stringfellow D. A. Murine leukemia: depressed response to interferon induction correlated with a serum hyporeactive factor. Infect Immun. 1976 Feb;13(2):392–398. doi: 10.1128/iai.13.2.392-398.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. 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]
  39. Törmä E. T., Paucker K. Purification and characterization of human leukocyte interferon components. J Biol Chem. 1976 Aug 25;251(16):4810–4816. [PubMed] [Google Scholar]
  40. Wheelock E. F. Interferon-like virus-inhibitor induced in human leukocytes by phytohemagglutinin. Science. 1965 Jul 16;149(3681):310–311. [PubMed] [Google Scholar]
  41. Wietzerbin J., Falcoff R., Catinot L., Falcoff E. Affinity chromatographic analysis of murine interferons induced by viruses and by T and B cell stimulants. Ann Immunol (Paris) 1977 Apr-Jun;128C(3):699–708. [PubMed] [Google Scholar]
  42. Winchester R. J., Fu S. M., Hoffman T., Kunkel H. G. IgG on lymphocyte surfaces; technical problems and the significance of a third cell population. J Immunol. 1975 Apr;114(4):1210–1212. [PubMed] [Google Scholar]
  43. Youngner J. S., Salvin S. B. Production and properties of migration inhibitory factor and interferon in the circulation of mice with delayed hypersensitivity. J Immunol. 1973 Dec;111(6):1914–1922. [PubMed] [Google Scholar]
  44. Youngner J. S., Stinebring W. R. Interferon appearance stimulated by endotoxin, bacteria, or viruses in mice pre-treated with Escherichia coli endotoxin or infected with Mycobacterium tuberculosis. Nature. 1965 Oct 30;208(5009):456–458. doi: 10.1038/208456a0. [DOI] [PubMed] [Google Scholar]

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