Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1991 Aug;59(8):2767–2773. doi: 10.1128/iai.59.8.2767-2773.1991

Potentiation of human natural killer cell cytotoxicity by Salmonella bacteria is an interferon- and interleukin-2-independent process that utilizes CD2 and CD18 structures in the effector phase.

J Tarkkanen 1, E Saksela 1
PMCID: PMC258085  PMID: 1713200

Abstract

Incubation of large granular lymphocytes (LGL) with glutaraldehyde-fixed bacteria stimulated in the supernatant the production of interferon (IFN), which proved to be mainly IFN-gamma. Even though IFN-gamma was produced upon exposure of LGL to bacteria, anti-IFN-gamma antibodies failed to interfere with induction of cytotoxicity by bacterial contact. Anti-IFN-gamma receptor antibodies had no effect on the induction of activated killing by bacterial contact either. We also tested the effect of anti-IFN-alpha antibody, but it failed to interfere with induction of cytotoxicity by bacterial contact. No interleukin-2 (IL-2) was detected in the culture supernatant of bacterially activated LGL by the mouse HT2 cell assay, nor did we detect any IL-2 mRNA in bacterially activated LGL by Northern RNA blot assay. Neutralizing anti-IL-2 antiserum had no effect on the induction of activated killing by bacterial contact, and recombinant IL-4 did not interfere with the induction of activated killing. We then studied the membrane structures involved in bacterially activated killing. Anti-CD18 monoclonal antibody did not interfere with the induction phase of bacterially activated killing. However, both anti-CD18 and anti-CD2 antibodies inhibited the effector phase of bacterially activated killing. The effector pathways utilized by activated LGL depended on the mode of activation in that even though bacterially activated LGL were sometimes blocked by anti-CD2 monoclonal antibody, recombinant-IL-2-stimulated LGL were not. In conclusion, our present results suggest that there may be mediators other than exogenously secreted IFNs and IL-2 which are responsible for the induction of activated killing after bacterial contact. CD18 and CD2 structures were shown to be involved in the effector phase of bacterially activated killing.

Full text

PDF
2767

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abo T., Sugawara S., Amenomori A., Itoh H., Rikiishi H., Moro I., Kumagai K. Selective phagocytosis of gram-positive bacteria and interleukin 1-like factor production by a subpopulation of large granular lymphocytes. J Immunol. 1986 May 1;136(9):3189–3197. [PubMed] [Google Scholar]
  2. Abo T., Sugawara S., Seki S., Fujii M., Rikiishi H., Takeda K., Kumagai K. Induction of human TCR gamma delta + and TCR gamma delta-CD2+CD3- double negative lymphocytes by bacterial stimulation. Int Immunol. 1990;2(8):775–785. doi: 10.1093/intimm/2.8.775. [DOI] [PubMed] [Google Scholar]
  3. Andersson L. C., Nilsson K., Gahmberg C. G. K562--a human erythroleukemic cell line. Int J Cancer. 1979 Feb;23(2):143–147. doi: 10.1002/ijc.2910230202. [DOI] [PubMed] [Google Scholar]
  4. Bandyopadhyay S., Perussia B., Trinchieri G., Miller D. S., Starr S. E. Requirement for HLA-DR+ accessory cells in natural killing of cytomegalovirus-infected fibroblasts. J Exp Med. 1986 Jul 1;164(1):180–195. doi: 10.1084/jem.164.1.180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bukowski J. F., Warner J. F., Dennert G., Welsh R. M. Adoptive transfer studies demonstrating the antiviral effect of natural killer cells in vivo. J Exp Med. 1985 Jan 1;161(1):40–52. doi: 10.1084/jem.161.1.40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bukowski J. F., Woda B. A., Habu S., Okumura K., Welsh R. M. Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo. J Immunol. 1983 Sep;131(3):1531–1538. [PubMed] [Google Scholar]
  7. Cuturi M. C., Murphy M., Costa-Giomi M. P., Weinmann R., Perussia B., Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med. 1987 Jun 1;165(6):1581–1594. doi: 10.1084/jem.165.6.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fitzgerald P. A., Mendelsohn M., Lopez C. Human natural killer cells limit replication of herpes simplex virus type 1 in vitro. J Immunol. 1985 Apr;134(4):2666–2672. [PubMed] [Google Scholar]
  9. Fujii M., Abo T., Kumagai K. Cytokines produced by blood mononuclear cells stimulated with the streptococcal preparation OK-432: effect on production by supplementing the medium with xenogeneic serum. Cancer Immunol Immunother. 1988;27(2):97–102. doi: 10.1007/BF00200011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Garcia-Peñarrubia P., Koster F. T., Kelley R. O., McDowell T. D., Bankhurst A. D. Antibacterial activity of human natural killer cells. J Exp Med. 1989 Jan 1;169(1):99–113. doi: 10.1084/jem.169.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  12. Hatcher F. M., Kuhn R. E. Destruction of Trypanosoma cruzi by Natural killer cells. Science. 1982 Oct 15;218(4569):295–296. doi: 10.1126/science.6812218. [DOI] [PubMed] [Google Scholar]
  13. Hauser W. E., Jr, Tsai V. Acute toxoplasma infection of mice induces spleen NK cells that are cytotoxic for T. gondii in vitro. J Immunol. 1986 Jan;136(1):313–319. [PubMed] [Google Scholar]
  14. Hedrick S. M., Cohen D. I., Nielsen E. A., Davis M. M. Isolation of cDNA clones encoding T cell-specific membrane-associated proteins. Nature. 1984 Mar 8;308(5955):149–153. doi: 10.1038/308149a0. [DOI] [PubMed] [Google Scholar]
  15. Hercend T., Meuer S., Brennan A., Edson M. A., Acuto O., Reinherz E. L., Schlossman S. F., Ritz J. Identification of a clonally restricted 90 kD heterodimer on two human cloned natural killer cell lines. Its role in cytotoxic effector function. J Exp Med. 1983 Nov 1;158(5):1547–1560. doi: 10.1084/jem.158.5.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hidore M. R., Murphy J. W. Natural cellular resistance of beige mice against Cryptococcus neoformans. J Immunol. 1986 Dec 1;137(11):3624–3631. [PubMed] [Google Scholar]
  17. 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]
  18. Klimpel G. R., Niesel D. W., Asuncion M., Klimpel K. D. Natural killer cell activation and interferon production by peripheral blood lymphocytes after exposure to bacteria. Infect Immun. 1988 Jun;56(6):1436–1441. doi: 10.1128/iai.56.6.1436-1441.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Klimpel G. R., Niesel D. W., Klimpel K. D. Natural cytotoxic effector cell activity against Shigella flexneri-infected HeLa cells. J Immunol. 1986 Feb 1;136(3):1081–1086. [PubMed] [Google Scholar]
  20. Lanier L. L., Benike C. J., Phillips J. H., Engleman E. G. Recombinant interleukin 2 enhanced natural killer cell-mediated cytotoxicity in human lymphocyte subpopulations expressing the Leu 7 and Leu 11 antigens. J Immunol. 1985 Feb;134(2):794–801. [PubMed] [Google Scholar]
  21. Lanier L. L., Buck D. W., Rhodes L., Ding A., Evans E., Barney C., Phillips J. H. Interleukin 2 activation of natural killer cells rapidly induces the expression and phosphorylation of the Leu-23 activation antigen. J Exp Med. 1988 May 1;167(5):1572–1585. doi: 10.1084/jem.167.5.1572. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lanier L. L., Cwirla S., Federspiel N., Phillips J. H. Human natural killer cells isolated from peripheral blood do not rearrange T cell antigen receptor beta chain genes. J Exp Med. 1986 Jan 1;163(1):209–214. doi: 10.1084/jem.163.1.209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lanier L. L., Le A. M., Ding A., Evans E. L., Krensky A. M., Clayberger C., Phillips J. H. Expression of Leu-19 (NKH-1) antigen on IL 2-dependent cytotoxic and non-cytotoxic T cell lines. J Immunol. 1987 Apr 1;138(7):2019–2023. [PubMed] [Google Scholar]
  24. Lanier L. L., Le A. M., Phillips J. H., Warner N. L., Babcock G. F. Subpopulations of human natural killer cells defined by expression of the Leu-7 (HNK-1) and Leu-11 (NK-15) antigens. J Immunol. 1983 Oct;131(4):1789–1796. [PubMed] [Google Scholar]
  25. Lindemann R. A. Bacterial activation of human natural killer cells: role of cell surface lipopolysaccharide. Infect Immun. 1988 May;56(5):1301–1308. doi: 10.1128/iai.56.5.1301-1308.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lindemann R. A. Roles of interferon and cellular adhesion molecules in bacterial activation of human natural killer cells. Infect Immun. 1989 Jun;57(6):1702–1706. doi: 10.1128/iai.57.6.1702-1706.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Lipscomb M. F., Alvarellos T., Toews G. B., Tompkins R., Evans Z., Koo G., Kumar V. Role of natural killer cells in resistance to Cryptococcus neoformans infections in mice. Am J Pathol. 1987 Aug;128(2):354–361. [PMC free article] [PubMed] [Google Scholar]
  28. Lüderitz O., Galanos C., Risse H. J., Ruschmann E., Schlecht S., Schmidt G., Schulte-Holthausen H., Wheat R., Westphal O., Schlosshardt J. Structural relationship of Salmonella O and R antigens. Ann N Y Acad Sci. 1966 Jun 30;133(2):349–374. doi: 10.1111/j.1749-6632.1966.tb52376.x. [DOI] [PubMed] [Google Scholar]
  29. Mogensen K. E., Cantell K. Human leukocyte interferon: a role for disulphide bonds. J Gen Virol. 1974 Jan;22(1):95–103. doi: 10.1099/0022-1317-22-1-95. [DOI] [PubMed] [Google Scholar]
  30. Morgan D. R., DuPont H. L., Gonik B., Kohl S. Cytotoxicity of human peripheral blood and colostral leukocytes against Shigella species. Infect Immun. 1984 Oct;46(1):25–33. doi: 10.1128/iai.46.1.25-33.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Nagler A., Lanier L. L., Phillips J. H. The effects of IL-4 on human natural killer cells. A potent regulator of IL-2 activation and proliferation. J Immunol. 1988 Oct 1;141(7):2349–2351. [PubMed] [Google Scholar]
  32. Nencioni L., Villa L., Boraschi D., Berti B., Tagliabue A. Natural and antibody-dependent cell-mediated activity against Salmonella typhimurium by peripheral and intestinal lymphoid cells in mice. J Immunol. 1983 Feb;130(2):903–907. [PubMed] [Google Scholar]
  33. Ortaldo J. R., Sharrow S. O., Timonen T., Herberman R. B. Determination of surface antigens on highly purified human NK cells by flow cytometry with monoclonal antibodies. J Immunol. 1981 Dec;127(6):2401–2409. [PubMed] [Google Scholar]
  34. Patarroyo M., Makgoba M. W. Leucocyte adhesion to cells. Molecular basis, physiological relevance, and abnormalities. Scand J Immunol. 1989 Aug;30(2):129–164. doi: 10.1111/j.1365-3083.1989.tb01197.x. [DOI] [PubMed] [Google Scholar]
  35. Perussia B., Trinchieri G., Jackson A., Warner N. L., Faust J., Rumpold H., Kraft D., Lanier L. L. The Fc receptor for IgG on human natural killer cells: phenotypic, functional, and comparative studies with monoclonal antibodies. J Immunol. 1984 Jul;133(1):180–189. [PubMed] [Google Scholar]
  36. Ritz J., Campen T. J., Schmidt R. E., Royer H. D., Hercend T., Hussey R. E., Reinherz E. L. Analysis of T-cell receptor gene rearrangement and expression in human natural killer clones. Science. 1985 Jun 28;228(4707):1540–1543. doi: 10.1126/science.2409597. [DOI] [PubMed] [Google Scholar]
  37. Roeder D. J., Lei M. G., Morrison D. C. Endotoxic-lipopolysaccharide-specific binding proteins on lymphoid cells of various animal species: association with endotoxin susceptibility. Infect Immun. 1989 Apr;57(4):1054–1058. doi: 10.1128/iai.57.4.1054-1058.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sheehan K. C., Calderon J., Schreiber R. D. Generation and characterization of monoclonal antibodies specific for the human IFN-gamma receptor. J Immunol. 1988 Jun 15;140(12):4231–4237. [PubMed] [Google Scholar]
  39. Tarkkanen J., Saksela E., Lanier L. L. Bacterial activation of human natural killer cells. Characteristics of the activation process and identification of the effector cell. J Immunol. 1986 Oct 15;137(8):2428–2433. [PubMed] [Google Scholar]
  40. Tarkkanen J., Saxén H., Nurminen M., Mäkelä P. H., Saksela E. Bacterial induction of human activated lymphocyte killing and its inhibition by lipopolysaccharide (LPS). J Immunol. 1986 Apr 1;136(7):2662–2669. [PubMed] [Google Scholar]
  41. Testi R., Phillips J. H., Lanier L. L. Leu 23 induction as an early marker of functional CD3/T cell antigen receptor triggering. Requirement for receptor cross-linking, prolonged elevation of intracellular [Ca++] and stimulation of protein kinase C. J Immunol. 1989 Mar 15;142(6):1854–1860. [PubMed] [Google Scholar]
  42. 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]
  43. Trinchieri G., Perussia B. Human natural killer cells: biologic and pathologic aspects. Lab Invest. 1984 May;50(5):489–513. [PubMed] [Google Scholar]
  44. Wright S. D., Jong M. T. Adhesion-promoting receptors on human macrophages recognize Escherichia coli by binding to lipopolysaccharide. J Exp Med. 1986 Dec 1;164(6):1876–1888. doi: 10.1084/jem.164.6.1876. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Zarling J. M., Clouse K. A., Biddison W. E., Kung P. C. Phenotypes of human natural killer cell populations detected with monoclonal antibodies. J Immunol. 1981 Dec;127(6):2575–2580. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES