Summary
This paper describes the influence of human fibroblast interferon (IFN-β) on the cytotoxic activity of natural killer cells (NK) in vitro and in vivo using the blood of healthy donors and myeloma patients. IFN-β stimulates NK activity against all target cells tested in vitro in a dose-dependent way up to 250% of pretreatment values. At higher IFN concentrations, stimulation returned to baseline values. Stimulation was most pronounced in the lowest lymphocyte to target cell ratio. 1- to 2-h preincubation of effector cells with IFN was enough to achieve maximal stimulation. The effector cells of IFN-treated myeloma-patients, or patients with herpes zoster, showed a clear reduction of toxicity against all cells tested during the first infusion, as compared to the pretreatment values.
Zusammenfassung
Die zytotoxische Aktivität der natürlichen Killerzellen (NK) wurde bei gesunden Spendern und Patienten mit Plasmocytom unter dem Einfluß von humanem Fibroblasteninterferon (IFN-β) in vitro und in vivo gemessen. IFN-β steigerte die NK-Aktivität gegenüber allen getesteten Zielzellen in vitro dosisabhängig bis zu 250% des Ausgangswertes. Bei weiterer Erhöhung der IFN-Konzentration nahm die Stimulation wieder ab. Die Stimulation war bei niedriger Lymphozyten-Zielzell-Relation am deutlichsten zu sehen. Eine 1- bis 2stündige Präinkubation der Effektorzellen mit Interferon reichte aus, um die maximale Stimulation zu erreichen. Wurde der Einfluß von IFN-β auf NK-Zellen in vivo im Blut von Interferon-behandelten Patienten mit Plasmocytom gemessen, zeigte sich eine deutliche Verminderung der Toxizität gegenüber allen getesteten Zielzellen während der ersten Infusion im Vergleich mit dem Ausgangswert vor Interferon-Therapie.
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References
Attallah AM, Folks T (1979) Interferon enhanced human natural killer and antibody-dependent cell-mediated cytotoxic activity. Int Arch Allergy Appl Immunol 60:377–382
Goutner A, Bruley-Rosset M, Florentin I, Misset JL, Mathe G (1981) Effect of long-term administration of interferon activity in myeloma patients and in mice. AACR Abstracts 291
Herberman RB, Nunn ME, Holden HI, Staal S, Djeu JY (1977) Augmentation of natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic target cells. Int J Cancer 19:555
Herberman RR, Ortaldo JR, Bonnard GD (1979) Augmentation by interferon of human natural and antibody-dependent cell-mediated cytotoxicity. Nature 277:221–223
Hochman PS, Cudkowicz G, Dausset J (1978) Decline of natural killer cell activity in sublethally irradiated mice. J Natl Cancer Inst 61:265
Huddlestone JR, Merigan TC, Oldstone MBA (1979) Induction and kinetics of natural killer cells. Nature 282:417–419
Janiaud P, Lecalvez J, Aubert Ch (1973) Characterisation cytoenzymologique des cellules de melanomes cutanées humaines en culture. Ann Dermatol Syphiligr (Paris) 100:536
Kiessling R, Hochman PS, Haller O, Shearer GM, Wigzell H, Cudkowicz G (1977) Evidence for a similar or a common mechanism for natural killer cell activity and resistance to hemopoietic grafts. Eur J Immunol 7:655
Leibold W, Janotte G, Peter HH (1980) Spontaneous cell-mediated cytotoxicity (SCMC) in various mammalian species and chickens: selective reaction pattern and different mechanisms. Scand J Immunol 11:203–222
Leibold W, Peter HH (1978) Spontaneous cell mediated cytotoxicity (SCMC): Another immune defense system. Behring Inst Mitt 62:144–172
Lozzio BB, Lozzio CB (1979) Properties and usefulness of the original K-562 human myelogenous leukemia cell line. Leuk Res 3:363–370
Masucci MG, Szigeti R, Klein E, Klein G, Gruest J, Montagnier L, Taira H, Hall A, Nagata S, Weissmann Ch (1980) Effect of interferon —α1 from E. coli on some cell functions. Science 209:1431–1435
Nilsson K (1971) Characteristics of established myeloma and lymphoblastoid cell lines derived from an IgE myeloma patient: a comparative study. Int J Cancer 7:380–396
Pape GR, Hadam MR, Eisenburg J, Riethmüller G (1981) Kinetics of natural cytotoxicity in patients treated with human fibroblast interferon. Cancer Immunol Immunother 11:1–6
Parkman R, Rosen FS (1976) Identification of a subpopulation of lymphocytes in human peripheral blood cytotoxic to autologous fibroblasts. J Exp Med 144:1520
Peter HH, Eife RF, Kalden JR (1976) Spontaneous cytotoxicity (SCMC) of normal human lymphocytes against a human melanoma cell line: a phenomenon due to a lymphotoxin-like mediator. J Immunol 116:342–348
Saksela E, Timonen T, Cantell K (1979) Human natural killer cell activity is augmented by interferon via recruitment of “pre-NK” cells. Scand J Immunol 10:257–266
Saksela E, Timonen T, Ranki A, Häyry P (1979) Morphological and functional characterization of isolated effector cells responsible for human natural killer activity to fetal fibroblasts and to cultured cell line targets. Immunol Rev 44:71–123
Stewart WE II (1979) The interferon system. Springer, Wien New York
Trinchieri G, Santoli D (1978) 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:1314–1333
Vilcek J, Gresser I, Merigan TC (eds) (1980) Regulatory functions of interferons. Ann NY Acad Sci 350:1–167
Zarling JM, Eskra L, Borden EC, Horoszewicz J, Carter WA (1979) Activation of human natural killer cells cytotoxic for human leukemia cells by purified interferon. J Immunol 123:63–70
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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft (Wa 139/13-4)
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Heidemann, E., Reichmann, U., Wilms, K. et al. Effect of human fibroblast interferon on natural killer cell activity: Stimulation in vitro and inhibition in vivo. Klin Wochenschr 60, 625–629 (1982). https://doi.org/10.1007/BF01711438
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DOI: https://doi.org/10.1007/BF01711438