Summary
Even though the enhancement of the lyitc capacity and the kinetics of lysis of natural killer cells (NK) by interferon has been well documented, an increase of the target-effector cell binding percentage is still disputed. We, therefore, modified the Grimm-Bonavida single-cell assay so that 400 to 600 cells per individual determination could be reliably evaluated. Using this assay, which makes possible separate determination of effector-target cell binding and target lysis, we demonstrated that, in addition to lytic capacity, target-effector cell binding is also increased by preincubating NK with 100 to 1,000 IU interferon alpha 2 per 106 cells. Our data indicate that interferon alpha 2 induces pre-NK cells to bind target cells and that it activates these pre-NK cells to kill the targets.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Abbreviations
- NK:
-
Natural killer cells
- LCMV:
-
Lymphocytic choriomeningitis virus
- IFN:
-
Interferon
- FCS:
-
Fetal calf serum
- RPMI 1640:
-
Culture medium
References
Biron CA, Turgiss LR, Welsh RM (1983) Increase in NK-cell number and turnover rate during acute viral infection. J Immunol 131:1539–1545
Bukowski JF, Biron CA, Welsh RM (1983) Elevated natural killer cell-mediated cytotoxicity, plasma interferon and tumor cell rejection in mice persistently infected with lymphocytic choriomeningitis virus. J Immunol 131:991–996
Claeys H, v. Damme J, de Ley M, Vermylen C (1982) Activation of natural cytotoxicity of human peripheral blood mononuclear cells by interferon: a kinetic study of different interferon types. Brit J Haematol 50:85–94
Djeu JY, Heinbaugh JA, Holden HT, Herberman RB (1978) Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J Immunol 122:178–181
Domzig W, Stadler MM, Herberman RB (1983) Interleukin 2 dependence of human natural killer cell activity. J Immunol 130:1970–1973
Grimm E, Bonavida B (1979) Mechanism of cell-mediated cytotoxicity at the single cell level: I. Estimation of cytotoxic T lymphocytes and relative lytic activity. J Immunol 123:2861–2869
Heidemann E, Reichmann U, Wilms K, Treuner J, Niethammer D (1982) Effect of human fibroblast interferon on natural killer cell activity: stimulation in vitro and inhibition in vivo. Klin Wochenschr 60:625–629
Herberman RB, Nunn ME, Holder HT, Lavrin DH (1975) Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors: II. Characterization of effector cells. Int J Cancer 16:230–239
Hersey P (1979) Natural killer cells: a new cytotoxic mechanism against tumers. Aust NZ J Med 9:464–472
Lotzova E, Savary CA, Gutterman JU, Hersh EM (1982) Modulation of natural killer cell-mediated cytotoxicity by partially purified and cloned interferon-alpha. Cancer Res 42:2480–2488
Lozzio CB, Lozzio BB (1975) Human chronic myelogeneous leukemia cell-line with positive Philadelphia-chromosome. Blood 45:321–334
Mathews PM, Froelich CJ, Sibbitt WL, Bankhurst AD (1983) Enhancement of natural cytotoxicity by beta-endophin. J Immunol 130:1658–1662
Oehler JR, Herberman RB (1978) Natural cell-mediated cytotoxicity in rats: III. Effects of immunopharmacological treatments on natural reactivity and on reactivity augmented by polyinosinic-polycytidilic acid. Int J Cancer 21:221–229
Ortaldo JR, Sharrow SO, Timonen T, Herberman RB (1981) Determination of surface antigens on highly purified human natural killer cells by flow cytometry by monoclonal antibody. J Immunol 127:2401–2409
Silva A, Bonavida B, Targan SR (1980) Mode of action of interferon-mediated modulation of natural killer cytotoxic activity: recruitment of pre-NK-cells and enhancement of kinetics of lysis. J Immunol 125:479–484
Stewart LD, Hinson A, Ades EW (1982) Enhanced binding and functional activity of human natural killer cells after interferon treatment. Clin Immunol Immunopathol 25:133–138
Targan SR, Dorey F (1980) Interferon activation of “Prespontaneous killer” (Pre-SK) cells and alteration in kinetics of lysis of both “Pre-SK” and active SK cells. J Immunol 124:2157–2161
Targan SR, Britvain L, Dorey F (1982) Activation of human NKCC by moderate exercise: increased frequency of NK cells with enhanced capability of effector-target lytic interactions. Clin Exp Immunol 45:352–360
Timonen T, Ortaldo JR, Herberman RB (1982) Analysis by a single cell cytotoxicity assay of natural killer (NK) cell frequencies among human large granular lymphocytes and of the effects of interferon on their activity. J Immunol 128:2514–2521
Welsh RM (1981) Natural cell-mediated immunity during viral infections. Curr Top Microbiol Immunol 92:83–106
Author information
Authors and Affiliations
Additional information
Dedicated to Prof. H.D. Waller on the occasion of his 60th birthday
Rights and permissions
About this article
Cite this article
Heidemann, E., Weber, J., Schmidt, H. et al. Recombinant interferon alpha 2 stimulation of target-binding by natural killer cells. Klin Wochenschr 64, 1036–1040 (1986). https://doi.org/10.1007/BF01757211
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01757211