Abstract
The relationship between the killing mechanisms of human natural killer (NK) cells, mitogen- and mixed-lymphocyte-culture-induced activated lymphocyte killer (ALK) cells, and monocytes was investigated with a monoclonal antibody. The IgG2 antibody 9.1C3 was prepared from mice immunized with purified human large granular lymphocytes and selected from clones that inhibited NK cell killing. The 9.1C3 antibody bound to all mononuclear cells but not to granulocytes or K562 cells, and it selectively blocked killing of K562 targets by both NK and ALK cells without affecting the binding of effector to target cells. The antibody blocked killing when present from time zero and it still inhibited partially even when added 1 hr after initiation of the lytic reaction. Killing of Epstein-Barr virus-transformed B lymphoblasts by classical cytotoxic T lymphocytes was not inhibited. Of interest, 9.1C3 did block the killing of K562 target cells by cultured peripheral blood monocytes. Other monoclonal antibodies that bound to monocytes did not block killing, and a nonspecific effect of the antibody on monocytes was excluded. These data suggest that NK cells, ALK cells, and monocytes can kill tumor cell targets by using similar lytic mechanisms.
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- Baum L. L., James K. K., Glaviano R. R., Gewurz H. Possible role for C-reactive protein in the human natural killer cell response. J Exp Med. 1983 Jan 1;157(1):301–311. doi: 10.1084/jem.157.1.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bloom B. R. Natural killers to rescue immune surveillance? Nature. 1982 Nov 18;300(5889):214–215. doi: 10.1038/300214a0. [DOI] [PubMed] [Google Scholar]
- Burnet F. M. Immunological surveillance in neoplasia. Transplant Rev. 1971;7:3–25. doi: 10.1111/j.1600-065x.1971.tb00461.x. [DOI] [PubMed] [Google Scholar]
- Burns G. F., Battye F. L., Goldstein G. Surface antigen changes occurring in short-term cultures of activated human T lymphocytes: analysis by flow cytometry. Cell Immunol. 1982 Jul 15;71(1):12–26. doi: 10.1016/0008-8749(82)90492-0. [DOI] [PubMed] [Google Scholar]
- Burns G. F., Boyd A. W., Beverley P. C. Two monoclonal anti-human T lymphocyte antibodies have similar biologic effects and recognize the same cell surface antigen. J Immunol. 1982 Oct;129(4):1451–1457. [PubMed] [Google Scholar]
- Chang T. W., Kung P. C., Gingras S. P., Goldstein G. Does OKT3 monoclonal antibody react with an antigen-recognition structure on human T cells? Proc Natl Acad Sci U S A. 1981 Mar;78(3):1805–1808. doi: 10.1073/pnas.78.3.1805. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Charriaut C., Senik A., Kolb J. P., Barel M., Frade R. Inhibition of in vitro natural killer activity by the third component of complement: role for the C3a fragment. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6003–6007. doi: 10.1073/pnas.79.19.6003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fast L. D., Hansen J. A., Newman W. Evidence for T cell nature and heterogeneity within natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC) effectors: a comparison with cytolytic T lymphocytes (CTL). J Immunol. 1981 Aug;127(2):448–452. [PubMed] [Google Scholar]
- Grimm E. A., Ramsey K. M., Mazumder A., Wilson D. J., Djeu J. Y., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. II. Precursor phenotype is serologically distinct from peripheral T lymphocytes, memory cytotoxic thymus-derived lymphocytes, and natural killer cells. J Exp Med. 1983 Mar 1;157(3):884–897. doi: 10.1084/jem.157.3.884. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hudig D., Haverty T., Fulcher C., Redelman D., Mendelsohn J. Inhibition of human natural cytotoxicity by macromolecular antiproteases. J Immunol. 1981 Apr;126(4):1569–1574. [PubMed] [Google Scholar]
- Kay H. D., Horwitz D. A. Evidence by reactivity with hybridoma antibodies for a probable myeloid origin of peripheral blood cells active in natural cytotoxicity and antibody-dependent cell-mediated cytotoxicity. J Clin Invest. 1980 Oct;66(4):847–851. doi: 10.1172/JCI109923. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Masucci M. G., Klein E., Argov S. Disappearance of the NK effect after explantation of lymphocytes and generation of similar nonspecific cytotoxicity correlated to the level of blastogenesis in activated cultures. J Immunol. 1980 May;124(5):2458–2463. [PubMed] [Google Scholar]
- Matthews N. Effect of human monocyte killing of tumour cells of antibody raised against an extracellular monocyte cytotoxin. Immunology. 1983 Feb;48(2):321–327. [PMC free article] [PubMed] [Google Scholar]
- Newman W. Selective blockade of human natural killer cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1982 Jun;79(12):3858–3862. doi: 10.1073/pnas.79.12.3858. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pawelec G. P., Hadam M. R., Ziegler A., Lohmeyer J., Rehbein A., Kumbier I., Wernet P. Long-term culture, cloning, and surface markers of mixed leukocyte culture-derived human T lymphocytes with natural killer-like cytotoxicity. J Immunol. 1982 Apr;128(4):1892–1896. [PubMed] [Google Scholar]
- Reinherz E. L., Meuer S., Fitzgerald K. A., Hussey R. E., Levine H., Schlossman S. F. Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex. Cell. 1982 Oct;30(3):735–743. doi: 10.1016/0092-8674(82)90278-1. [DOI] [PubMed] [Google Scholar]
- Seeley J. K., Masucci G., Poros A., Klein E., Golub S. H. Studies on cytotoxicity generated in human mixed lymphocyte cultures. II. Anti-K562 effectors are distinct from allospecific CTL and can be generated from NK-depleted T cells. J Immunol. 1979 Sep;123(3):1303–1311. [PubMed] [Google Scholar]
- Strassmann G., Bach F. H., Zarling J. M. Depletion of human NK cells with monoclonal antibodies allows the generation of cytotoxic T lymphocytes without NK-like cells in mixed cultures. J Immunol. 1983 Apr;130(4):1556–1560. [PubMed] [Google Scholar]
- Timonen T., Saksela E. Isolation of human NK cells by density gradient centrifugation. J Immunol Methods. 1980;36(3-4):285–291. doi: 10.1016/0022-1759(80)90133-7. [DOI] [PubMed] [Google Scholar]
- Wallace L. E., Rickinson A. B., Rowe M., Moss D. J., Allen D. J., Epstein M. A. Stimulation of human lymphocytes with irradiated cells of the autologous Epstein-Barr virus-transformed cell line. I. Virus-specific and nonspecific components of the cytotoxic response. Cell Immunol. 1982 Feb;67(1):129–140. doi: 10.1016/0008-8749(82)90205-2. [DOI] [PubMed] [Google Scholar]
- Wright S. C., Bonavida B. YAC-1 variant clones selected for resistance to natural killer cytotoxic factors are also resistant to natural killer cell-mediated cytotoxicity. Proc Natl Acad Sci U S A. 1983 Mar;80(6):1688–1692. doi: 10.1073/pnas.80.6.1688. [DOI] [PMC free article] [PubMed] [Google Scholar]

