Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1992 Dec 1;176(6):1511–1519. doi: 10.1084/jem.176.6.1511

Human lymphokine-activated killer cells are cytotoxic against cells infected with Toxoplasma gondii

PMCID: PMC2119447  PMID: 1460415

Abstract

Experiments were conducted to determine whether human lymphokine- activated killer (LAK) cells are cytotoxic against cells infected with Toxoplasma gondii. Nylon wool nonadherent (NWNA) peripheral blood lymphocytes, as well as purified natural killer cell (NK) (CD3- CD16+ CD56+) and T (CD3+ CD16- CD56-) cells obtained from five healthy T. gondii seronegative volunteers exhibited minimal cytotoxic activity against T. gondii-infected cells. When standard LAK (S-LAK) cell preparations were induced by incubation of NWNA cells with recombinant interleukin 2, induction of remarkable cytotoxic activity against T. gondii-infected cells. When standard in LAK cell preparations from each of the volunteers. The phenotype of the LAK precursor and effector cells varied depending on the target cell used. Whereas the precursor and the effector cells of most of the LAK activity against K562 and Daudi cells were cells with NK phenotype, when T. gondii-infected cells were used as targets, both cells with NK and T cell phenotypes were precursors and effectors of the lysis. When cytotoxic activity of S-LAK cells was compared with the activity of adherent LAK (A-LAK) cells, A- LAK cells displayed higher cytotoxic activity against T. gondii- infected cells, as well as against K562 and Daudi cells. Cold target inhibition experiments suggested that there is a subset of LAK effector cells capable of lysing both T. gondii-infected cells and Daudi cells, whereas other subsets preferentially or exclusively lyse one of these target cells.

Full Text

The Full Text of this article is available as a PDF (845.2 KB).

Selected References

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

  1. Anderson S. E., Jr, Remington J. S. Effect of normal and activated human macrophages on Toxoplasma gondii. J Exp Med. 1974 May 1;139(5):1154–1174. doi: 10.1084/jem.139.5.1154. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ballas Z. K., Rasmussen W. Lymphokine-activated killer (LAK) cells. IV. Characterization of murine LAK effector subpopulations. J Immunol. 1990 Jan 1;144(1):386–395. [PubMed] [Google Scholar]
  3. Ballas Z. K., Rasmussen W., van Otegham J. K. Lymphokine-activated killer (LAK) cells. II. Delineation of distinct murine LAK-precursor subpopulations. J Immunol. 1987 Mar 1;138(5):1647–1652. [PubMed] [Google Scholar]
  4. Blanchard D. K., Michelini-Norris M. B., Friedman H., Djeu J. Y. Lysis of mycobacteria-infected monocytes by IL-2-activated killer cells: role of LFA-1. Cell Immunol. 1989 Apr 1;119(2):402–411. doi: 10.1016/0008-8749(89)90254-2. [DOI] [PubMed] [Google Scholar]
  5. Blanchard D. K., Stewart W. E., 2nd, Klein T. W., Friedman H., Djeu J. Y. Cytolytic activity of human peripheral blood leukocytes against Legionella pneumophila-infected monocytes: characterization of the effector cell and augmentation by interleukin 2. J Immunol. 1987 Jul 15;139(2):551–556. [PubMed] [Google Scholar]
  6. Bukowski J. F., Yang H., Welsh R. M. Antiviral effect of lymphokine-activated killer cells: characterization of effector cells mediating prophylaxis. J Virol. 1988 Oct;62(10):3642–3648. doi: 10.1128/jvi.62.10.3642-3648.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Carl M., Dasch G. A. Characterization of human cytotoxic lymphocytes directed against cells infected with typhus group rickettsiae: evidence for lymphokine activation of effectors. J Immunol. 1986 Apr 1;136(7):2654–2661. [PubMed] [Google Scholar]
  8. Dannemann B. R., Morris V. A., Araujo F. G., Remington J. S. Assessment of human natural killer and lymphokine-activated killer cell cytotoxicity against Toxoplasma gondii trophozoites and brain cysts. J Immunol. 1989 Oct 15;143(8):2684–2691. [PubMed] [Google Scholar]
  9. Desmonts G., Remington J. S. Direct agglutination test for diagnosis of Toxoplasma infection: method for increasing sensitivity and specificity. J Clin Microbiol. 1980 Jun;11(6):562–568. doi: 10.1128/jcm.11.6.562-568.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Froelich C. J., Guiffaut S. Lysis of human T cell leukemia virus infected T and B lymphoid cells by interleukin 2-activated killer cells. J Immunol. 1987 Dec 1;139(11):3637–3643. [PubMed] [Google Scholar]
  11. Gazzinelli R. T., Hakim F. T., Hieny S., Shearer G. M., Sher A. Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. J Immunol. 1991 Jan 1;146(1):286–292. [PubMed] [Google Scholar]
  12. Grimm E. A., Mazumder A., Zhang H. Z., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982 Jun 1;155(6):1823–1841. doi: 10.1084/jem.155.6.1823. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gunji Y., Vujanovic N. L., Hiserodt J. C., Herberman R. B., Gorelik E. Generation and characterization of purified adherent lymphokine-activated killer cells in mice. J Immunol. 1989 Mar 1;142(5):1748–1754. [PubMed] [Google Scholar]
  14. Hakim F. T., Gazzinelli R. T., Denkers E., Hieny S., Shearer G. M., Sher A. CD8+ T cells from mice vaccinated against Toxoplasma gondii are cytotoxic for parasite-infected or antigen-pulsed host cells. J Immunol. 1991 Oct 1;147(7):2310–2316. [PubMed] [Google Scholar]
  15. 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]
  16. Haverkos H. W. Assessment of therapy for toxoplasma encephalitis. The TE Study Group. Am J Med. 1987 May;82(5):907–914. doi: 10.1016/0002-9343(87)90151-3. [DOI] [PubMed] [Google Scholar]
  17. Hughes H. P., Kasper L. H., Little J., Dubey J. P. Absence of a role for natural killer cells in the control of acute infection by Toxoplasma gondii oocysts. Clin Exp Immunol. 1988 Jun;72(3):394–399. [PMC free article] [PubMed] [Google Scholar]
  18. Jemma C., Cignetti A., Geuna M., Caretto P., Vai S., Forni G. In vitro and in vivo comparison of the activity of human lymphokine-activated killer (LAK) cells and adherent LAK cells. J Immunother (1991) 1991 Jun;10(3):189–199. doi: 10.1097/00002371-199106000-00005. [DOI] [PubMed] [Google Scholar]
  19. Lafreniere R., Rosenberg S. A. Adoptive immunotherapy of murine hepatic metastases with lymphokine activated killer (LAK) cells and recombinant interleukin 2 (RIL 2) can mediate the regression of both immunogenic and nonimmunogenic sarcomas and an adenocarcinoma. J Immunol. 1985 Dec;135(6):4273–4280. [PubMed] [Google Scholar]
  20. Lotzová E., Savary C. A., Totpal K., Schachner J., Lichtiger B., McCredie K. B., Freireich E. J. Highly oncolytic adherent lymphocytes: therapeutic relevance for leukemia. Leuk Res. 1991;15(4):245–254. doi: 10.1016/0145-2126(91)90127-f. [DOI] [PubMed] [Google Scholar]
  21. Mazumder A., Rosenberg S. A. Successful immunotherapy of natural killer-resistant established pulmonary melanoma metastases by the intravenous adoptive transfer of syngeneic lymphocytes activated in vitro by interleukin 2. J Exp Med. 1984 Feb 1;159(2):495–507. doi: 10.1084/jem.159.2.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Melder R. J., Walker E. R., Herberman R. B., Whiteside T. L. Surface characteristics, morphology, and ultrastructure of human adherent lymphokine-activated killer cells. J Leukoc Biol. 1990 Aug;48(2):163–173. doi: 10.1002/jlb.48.2.163. [DOI] [PubMed] [Google Scholar]
  23. Melder R. J., Whiteside T. L., Vujanovic N. L., Hiserodt J. C., Herberman R. B. A new approach to generating antitumor effectors for adoptive immunotherapy using human adherent lymphokine-activated killer cells. Cancer Res. 1988 Jun 15;48(12):3461–3469. [PubMed] [Google Scholar]
  24. Ortaldo J. R., Mason A., Overton R. Lymphokine-activated killer cells. Analysis of progenitors and effectors. J Exp Med. 1986 Oct 1;164(4):1193–1205. doi: 10.1084/jem.164.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Phillips J. H., Lanier L. L. Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis. J Exp Med. 1986 Sep 1;164(3):814–825. doi: 10.1084/jem.164.3.814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Rabinowich H., Sedlmayr P., Herberman R. B., Whiteside T. L. Increased proliferation, lytic activity, and purity of human natural killer cells cocultured with mitogen-activated feeder cells. Cell Immunol. 1991 Jul;135(2):454–470. doi: 10.1016/0008-8749(91)90290-r. [DOI] [PubMed] [Google Scholar]
  27. Resnick M., Roguel N., Bercovier H., Enk C., Frankenburg S., Kedar E. Lysis of murine macrophages infected with intracellular pathogens by interleukin 2-activated killer (LAK) cells in vitro. Cell Immunol. 1988 Apr 15;113(1):214–219. doi: 10.1016/0008-8749(88)90019-6. [DOI] [PubMed] [Google Scholar]
  28. Rosenberg S. A., Lotze M. T., Muul L. M., Chang A. E., Avis F. P., Leitman S., Linehan W. M., Robertson C. N., Lee R. E., Rubin J. T. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987 Apr 9;316(15):889–897. doi: 10.1056/NEJM198704093161501. [DOI] [PubMed] [Google Scholar]
  29. Rosenberg S. A., Lotze M. T., Muul L. M., Leitman S., Chang A. E., Ettinghausen S. E., Matory Y. L., Skibber J. M., Shiloni E., Vetto J. T. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985 Dec 5;313(23):1485–1492. doi: 10.1056/NEJM198512053132327. [DOI] [PubMed] [Google Scholar]
  30. Rosenstein M., Yron I., Kaufmann Y., Rosenberg S. A. Lymphokine-activated killer cells: lysis of fresh syngeneic natural killer-resistant murine tumor cells by lymphocytes cultured in interleukin 2. Cancer Res. 1984 May;44(5):1946–1953. [PubMed] [Google Scholar]
  31. Sabin A. B., Feldman H. A. Dyes as Microchemical Indicators of a New Immunity Phenomenon Affecting a Protozoon Parasite (Toxoplasma). Science. 1948 Dec 10;108(2815):660–663. doi: 10.1126/science.108.2815.660. [DOI] [PubMed] [Google Scholar]
  32. Schwarz R. E., Vujanovic N. L., Hiserodt J. C. Enhanced antimetastatic activity of lymphokine-activated killer cells purified and expanded by their adherence to plastic. Cancer Res. 1989 Mar 15;49(6):1441–1446. [PubMed] [Google Scholar]
  33. Sharma S. D., Catterall J. R., Remington J. S. Parasiticidal activity of macrophages against Toxoplasma. Methods Enzymol. 1986;132:626–637. doi: 10.1016/s0076-6879(86)32046-9. [DOI] [PubMed] [Google Scholar]
  34. Sharma S. D., Hofflin J. M., Remington J. S. In vivo recombinant interleukin 2 administration enhances survival against a lethal challenge with Toxoplasma gondii. J Immunol. 1985 Dec;135(6):4160–4163. [PubMed] [Google Scholar]
  35. Subauste C. S., Koniaris A. H., Remington J. S. Murine CD8+ cytotoxic T lymphocytes lyse Toxoplasma gondii-infected cells. J Immunol. 1991 Dec 1;147(11):3955–3959. [PubMed] [Google Scholar]
  36. Suzuki Y., Remington J. S. Dual regulation of resistance against Toxoplasma gondii infection by Lyt-2+ and Lyt-1+, L3T4+ T cells in mice. J Immunol. 1988 Jun 1;140(11):3943–3946. [PubMed] [Google Scholar]
  37. Tilden A. B., Itoh K., Balch C. M. Human lymphokine-activated killer (LAK) cells: identification of two types of effector cells. J Immunol. 1987 Feb 15;138(4):1068–1073. [PubMed] [Google Scholar]
  38. Timonen T., Patarroyo M., Gahmberg C. G. CD11a-c/CD18 and GP84 (LB-2) adhesion molecules on human large granular lymphocytes and their participation in natural killing. J Immunol. 1988 Aug 1;141(3):1041–1046. [PubMed] [Google Scholar]
  39. Wisseman C. L., Jr, Waddell A. Interferonlike factors from antigen- and mitogen-stimulated human leukocytes with antirickettsial and cytolytic actions on Rickettsia prowazekii. Infected human endothelial cells, fibroblasts, and macrophages. J Exp Med. 1983 Jun 1;157(6):1780–1793. doi: 10.1084/jem.157.6.1780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yano A., Aosai F., Ohta M., Hasekura H., Sugane K., Hayashi S. Antigen presentation by Toxoplasma gondii-infected cells to CD4+ proliferative T cells and CD8+ cytotoxic cells. J Parasitol. 1989 Jun;75(3):411–416. [PubMed] [Google Scholar]
  41. Zychlinsky A., Karim M., Nonacs R., Young J. D. A homogeneous population of lymphokine-activated killer (LAK) cells is incapable of killing virus-, bacteria-, or parasite-infected macrophages. Cell Immunol. 1990 Jan;125(1):261–267. doi: 10.1016/0008-8749(90)90080-b. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES