Abstract
Cell fractionation techniques were used to identify the cells in rat spleen responsible for natural killing of a syngeneic sarcoma cell in short-term (6 h and 18 h) and long-term (72 h) cytotoxicity assays. Cytotoxicity was quantified precisely using a method previously derived from consideration of natural cytotoxicity as an enzyme-substrate reaction, and by analysing results in terms of lytic units. Killing in all three assays displayed 'single-hit' kinetics implying that a single effector cell was sufficient to lyse a single target cell. The fractionation studies, using glass adherence, carbonyl iron, nylon wool, EA and EAC monolayers and congenitally athymic rats, revealed two populations of cytotoxic cells. In the 6 h assay most of the activity was due to cells with similar characteristics to the NK cells previously defined using leukaemic targets, but in the 18 h and 72 h assays macrophages played an important rôle. The activity exerted by the macrophages was cell lysis and not cytostasis. No evidence that the macrophages acted by releasing factors which stimulated NK cells could be found.
Full text
PDF







Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Boyle W. An extension of the 51Cr-release assay for the estimation of mouse cytotoxins. Transplantation. 1968 Sep;6(6):761–764. doi: 10.1097/00007890-196809000-00002. [DOI] [PubMed] [Google Scholar]
- Brooks C. G., Flannery G. R. Quantitative studies of natural immunity to solid tumours in rats. Persistence of natural immunity throughout reproductive life, and absence of suppressor cells in infant rats. Immunology. 1980 Feb;39(2):187–194. [PMC free article] [PubMed] [Google Scholar]
- Brooks C. G., Rees R. C., Leach R. H. High nonspecific reactivity of normal lymphocytes against mycoplasma-infected target cells in cytotoxicity assays. Eur J Immunol. 1979 Feb;9(2):159–165. doi: 10.1002/eji.1830090213. [DOI] [PubMed] [Google Scholar]
- Brooks C. G. Studies on the microcytotoxicity test. III. Comparison of [75Se]selenomethionine with [3H]proline, Na2, 51CrO4 and [125I]iododeoxyuridine for pre-labelling target cells in long-term cytotoxicity tests. J Immunol Methods. 1978;22(1-2):23–36. doi: 10.1016/0022-1759(78)90055-8. [DOI] [PubMed] [Google Scholar]
- Currie G. A., Basham C. Differential arginine dependence and the selective cytotoxic effects of activated macrophages for malignant cells in vitro. Br J Cancer. 1978 Dec;38(6):653–659. doi: 10.1038/bjc.1978.270. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Djeu J. Y., Heinbaugh J. A., Holden H. T., Herberman R. B. Role of macrophages in the augementation of mouse natural killer cell activity by poly I:C and interferon. J Immunol. 1979 Jan;122(1):182–188. [PubMed] [Google Scholar]
- Gomard E., Leclerc J. C., Levy J. P. Spontaneous antilymphoma reaction of preleukaemic AKR mice is a non-T-cell killing. Nature. 1974 Aug 23;250(5468):671–673. doi: 10.1038/250671a0. [DOI] [PubMed] [Google Scholar]
- Herberman R. B., Bartram S., Haskill J. S., Nunn M., Holden H. T., West W. H. Fc receptors on mouse effector cells mediating natural cytotoxicity against tumor cells. J Immunol. 1977 Jul;119(1):322–326. [PubMed] [Google Scholar]
- Herberman R. B., Holden H. T. Natural cell-mediated immunity. Adv Cancer Res. 1978;27:305–377. doi: 10.1016/s0065-230x(08)60936-7. [DOI] [PubMed] [Google Scholar]
- Herberman R. B., Nunn M. E., Holden H. T., Lavrin D. H. Natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogeneic tumors. II. Characterization of effector cells. Int J Cancer. 1975 Aug 15;16(2):230–239. doi: 10.1002/ijc.2910160205. [DOI] [PubMed] [Google Scholar]
- 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]
- Kedar E., Ortiz de Landazuri M., Bonavida B. Cellular immunoadsorbents: a simplified technique for separation of lymphoid cell populations. J Immunol. 1974 Mar;112(3):1231–1243. [PubMed] [Google Scholar]
- Keller R. Macrophage-mediated natrual cytotoxicity against various target cells in vitro. I. Macrophages from diverse anatomical sites and different strains of rats and mice. Br J Cancer. 1978 May;37(5):732–741. doi: 10.1038/bjc.1978.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kiessling R., Klein E., Pross H., Wigzell H. "Natural" killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Characteristics of the killer cell. Eur J Immunol. 1975 Feb;5(2):117–121. doi: 10.1002/eji.1830050209. [DOI] [PubMed] [Google Scholar]
- Lucas Z. J., Walker S. M. Cytotoxic activity of lymphocytes. 3. Standardization of measurement of cell-mediated lysis. J Immunol. 1974 Jul;113(1):209–224. [PubMed] [Google Scholar]
- Matthews N., Rolland J. M., Nairn R. C. Lymphoid cell fractionation by aggregated immunoglobulin-agarose columns. J Immunol Methods. 1976;9(3-4):323–335. doi: 10.1016/0022-1759(76)90207-6. [DOI] [PubMed] [Google Scholar]
- Meltzer M. S., Ruco L. P., Boraschi D., Nacy C. A. Macrophage activation for tumor cytotoxicity: analysis of intermediary reactions. J Reticuloendothel Soc. 1979 Oct;26(4):403–415. [PubMed] [Google Scholar]
- Nunn M. E., Herberman R. B., Holden H. T. Natural cell-mediated cytotoxicity in mice against non-lymphoid tumor cells and some normal cells. Int J Cancer. 1977 Sep 15;20(3):381–387. doi: 10.1002/ijc.2910200309. [DOI] [PubMed] [Google Scholar]
- Oehler J. R., Lindsay L. R., Nunn M. E., Herberman R. B. Natural cell-mediated cytotoxicity in rats. I. Tissue and strain distribution, and demonstration of a membrance receptor for the Fc portion of IgG. Int J Cancer. 1978 Feb 15;21(2):204–209. doi: 10.1002/ijc.2910210212. [DOI] [PubMed] [Google Scholar]
- Paige C. J., Figarella E. F., Cuttito M. J., Cahan A., Stutman O. Natural cytotoxic cells against solid tumors in mice. II. Some characteristics of the effector cells. J Immunol. 1978 Nov;121(5):1827–1835. [PubMed] [Google Scholar]
- Sendo F., Aoki T., Boyse E. A., Buafo C. K. Natural occurrence of lymphocytes showing cytotoxic activity to BALB/c radiation-induced leukemia RL male 1 cells. J Natl Cancer Inst. 1975 Sep;55(3):603–609. doi: 10.1093/jnci/55.3.603. [DOI] [PubMed] [Google Scholar]
- Shellam G. R. Gross-virus-induced lymphoma in the rat. V. Natural cytotoxic cells are non-T cells. Int J Cancer. 1977 Feb 15;19(2):225–235. doi: 10.1002/ijc.2910190212. [DOI] [PubMed] [Google Scholar]
- Stutman O., Paige C. J., Figarella E. F. Natural cytotoxic cells against solid tumors in mice. I. Strain and age distribution and target cell susceptibility. J Immunol. 1978 Nov;121(5):1819–1826. [PubMed] [Google Scholar]
- 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]
- Webb P. J., Brooks C. G. Macrophage-like suppressor cells in rats. I. Inhibition of natural macrophage-like suppressor cells by red blood cells. Cell Immunol. 1980 Jul 1;52(2):370–380. doi: 10.1016/0008-8749(80)90358-5. [DOI] [PubMed] [Google Scholar]