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. 1991 Sep;85(3):519–524. doi: 10.1111/j.1365-2249.1991.tb05760.x

Lymphokine-activated killer (LAK) cells modulate the effects of IL-2 on a T cell-mediated immune response.

P McCulloch 1, G Gallagher 1, L P Walsh 1, Y Zaloom 1, J Xie 1
PMCID: PMC1535602  PMID: 1893635

Abstract

The ability of LAK cells and/or IL-2 to affect the course of an established T cell response was examined in a delayed-type hypersensitivity (DTH) model. IL-2 greatly increased the magnitude of the response at 24 h, while LAK cells alone had no effect. The administration of LAK cells and IL-2 together also had no effect on the magnitude of the DTH response, demonstrating that LAK cells were able to remove the enhancement seen with IL-2 alone. The presence of LAK cells reduced the serum half-life of IL-2 significantly, but not to an extent able to account for the observed loss of IL-2 induced DTH enhancement. IL-2 administration influenced cell phenotypes in the spleen and draining lymph nodes (DLN), as well as increasing splenic weight; the additional presence of LAK cells markedly altered these effects of IL-2 in the spleen (but not the DLN). Taken together, these results suggest that LAK cells interact with activated T-cells within the immune system and modulate their function.

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Selected References

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  1. Al-Azzawi F., Stimson W. H., Govan A. D. Human antibodies to ovarian cancer antigens secreted by lymphoblastoid cell lines. J Clin Lab Immunol. 1987 Feb;22(2):71–75. [PubMed] [Google Scholar]
  2. Amigorena S., Bonnerot C., Fridman W. H., Teillaud J. L. Recombinant interleukin 2-activated natural killer cells regulate IgG2a production. Eur J Immunol. 1990 Aug;20(8):1781–1787. doi: 10.1002/eji.1830200824. [DOI] [PubMed] [Google Scholar]
  3. Brooks B., Rees R. C. Human recombinant IL-4 suppresses the induction of human IL-2 induced lymphokine activated killer (LAK) activity. Clin Exp Immunol. 1988 Nov;74(2):162–165. [PMC free article] [PubMed] [Google Scholar]
  4. Chang A. E., Hyatt C. L., Rosenberg S. A. Systemic administration of recombinant human interleukin-2 in mice. J Biol Response Mod. 1984 Oct;3(5):561–572. [PubMed] [Google Scholar]
  5. Cotran R. S., Pober J. S., Gimbrone M. A., Jr, Springer T. A., Wiebke E. A., Gaspari A. A., Rosenberg S. A., Lotze M. T. Endothelial activation during interleukin 2 immunotherapy. A possible mechanism for the vascular leak syndrome. J Immunol. 1988 Mar 15;140(6):1883–1888. [PubMed] [Google Scholar]
  6. Cozzolino F., Torcia M., Carossino A. M., Giordani R., Selli C., Talini G., Reali E., Novelli A., Pistoia V., Ferrarini M. Characterization of cells from invaded lymph nodes in patients with solid tumors. Lymphokine requirement for tumor-specific lymphoproliferative response. J Exp Med. 1987 Aug 1;166(2):303–318. doi: 10.1084/jem.166.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Eggermont A. M., Steller E. P., Matthews W., Sugarbaker P. H. Alloimmune cells consume interleukin-2 and competitively inhibit the anti-tumour effects of interleukin-2. Br J Cancer. 1987 Aug;56(2):97–102. doi: 10.1038/bjc.1987.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Essery G., Feldmann M., Lamb J. R. Interleukin-2 can prevent and reverse antigen-induced unresponsiveness in cloned human T lymphocytes. Immunology. 1988 Jul;64(3):413–417. [PMC free article] [PubMed] [Google Scholar]
  9. Ettinghausen S. E., Lipford E. H., 3rd, Mulé J. J., Rosenberg S. A. Systemic administration of recombinant interleukin 2 stimulates in vivo lymphoid cell proliferation in tissues. J Immunol. 1985 Aug;135(2):1488–1497. [PubMed] [Google Scholar]
  10. Gallagher G., Findlay J., al-Azzawi F. A. Human lymphokine-activated killer cells develop syngeneic killing ability. Immunology. 1989 Mar;66(3):471–474. [PMC free article] [PubMed] [Google Scholar]
  11. Gallagher G., al-Azzawi F., Davis J., Stimson W. H. Cytokines regulate the ability of human LAK-cells to kill human tumour cells in vitro. Br J Cancer. 1989 Jun;59(6):919–921. doi: 10.1038/bjc.1989.194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gallagher G., al-Azzawi F., Walsh L. P., Wilson G. 14C1, an antigen associated with human ovarian cancer, defined using a human IgG monoclonal antibody. Clin Exp Immunol. 1991 Jan;83(1):92–95. doi: 10.1111/j.1365-2249.1991.tb05594.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gemlo B. T., Palladino M. A., Jr, Jaffe H. S., Espevik T. P., Rayner A. A. Circulating cytokines in patients with metastatic cancer treated with recombinant interleukin 2 and lymphokine-activated killer cells. Cancer Res. 1988 Oct 15;48(20):5864–5867. [PubMed] [Google Scholar]
  14. Grimm E. A., Robb R. J., Roth J. A., Neckers L. M., Lachman L. B., Wilson D. J., Rosenberg S. A. Lymphokine-activated killer cell phenomenon. III. Evidence that IL-2 is sufficient for direct activation of peripheral blood lymphocytes into lymphokine-activated killer cells. J Exp Med. 1983 Oct 1;158(4):1356–1361. doi: 10.1084/jem.158.4.1356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Guillou P. J., Ramsden C. W., Somers S. S., Sedman P. C. Suppression of the generation of lymphokine-activated killer (LAK) cells by serum-free supernatants of in vitro maintained tumour cell lines. Br J Cancer. 1989 Apr;59(4):515–521. doi: 10.1038/bjc.1989.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kornfeld H., Berman J. S., Beer D. J., Center D. M. Induction of human T lymphocyte motility by interleukin 2. J Immunol. 1985 Jun;134(6):3887–3890. [PubMed] [Google Scholar]
  17. Lotze M. T., Finn O. J. Recent advances in cellular immunology: implications for immunity to cancer. Immunol Today. 1990 Jun;11(6):190–193. doi: 10.1016/0167-5699(90)90079-o. [DOI] [PubMed] [Google Scholar]
  18. Lotze M. T., Line B. R., Mathisen D. J., Rosenberg S. A. The in vivo distribution of autologous human and murine lymphoid cells grown in T cell growth factor (TCGF): implications for the adoptive immunotherapy of tumors. J Immunol. 1980 Oct;125(4):1487–1493. [PubMed] [Google Scholar]
  19. Lotze M. T., Matory Y. L., Ettinghausen S. E., Rayner A. A., Sharrow S. O., Seipp C. A., Custer M. C., Rosenberg S. A. In vivo administration of purified human interleukin 2. II. Half life, immunologic effects, and expansion of peripheral lymphoid cells in vivo with recombinant IL 2. J Immunol. 1985 Oct;135(4):2865–2875. [PubMed] [Google Scholar]
  20. Malkovský M., Loveland B., North M., Asherson G. L., Gao L., Ward P., Fiers W. Recombinant interleukin-2 directly augments the cytotoxicity of human monocytes. Nature. 1987 Jan 15;325(6101):262–265. doi: 10.1038/325262a0. [DOI] [PubMed] [Google Scholar]
  21. Malkovský M., Medawar P. B., Thatcher D. R., Toy J., Hunt R., Rayfield L. S., Doré C. Acquired immunological tolerance of foreign cells is impaired by recombinant interleukin 2 or vitamin A acetate. Proc Natl Acad Sci U S A. 1985 Jan;82(2):536–538. doi: 10.1073/pnas.82.2.536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Morahan G., Allison J., Miller J. F. Tolerance of class I histocompatibility antigens expressed extrathymically. Nature. 1989 Jun 22;339(6226):622–624. doi: 10.1038/339622a0. [DOI] [PubMed] [Google Scholar]
  23. Mulé J. J., Shu S., Rosenberg S. A. The anti-tumor efficacy of lymphokine-activated killer cells and recombinant interleukin 2 in vivo. J Immunol. 1985 Jul;135(1):646–652. [PubMed] [Google Scholar]
  24. Mulé J. J., Yang J. C., Afreniere R. L., Shu S. Y., Rosenberg S. A. Identification of cellular mechanisms operational in vivo during the regression of established pulmonary metastases by the systemic administration of high-dose recombinant interleukin 2. J Immunol. 1987 Jul 1;139(1):285–294. [PubMed] [Google Scholar]
  25. Rosenberg S. A., Spiess P. J., Schwarz S. In vivo administration of Interleukin-2 enhances specific alloimmune responses. Transplantation. 1983 Jun;35(6):631–634. doi: 10.1097/00007890-198306000-00024. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Rubin J. T., Elwood L. J., Rosenberg S. A., Lotze M. T. Immunohistochemical correlates of response to recombinant interleukin-2-based immunotherapy in humans. Cancer Res. 1989 Dec 15;49(24 Pt 1):7086–7092. [PubMed] [Google Scholar]
  28. Silagi S., Dutkowski R., Schaefer A. In vivo requirement for asialo GM1 and Thy1 positive leukocytes for antitumor effect of rIL-2 +/- rIFN-gamma. Anticancer Res. 1988 Nov-Dec;8(6):1265–1269. [PubMed] [Google Scholar]
  29. Topalian S. L., Muul L. M., Solomon D., Rosenberg S. A. Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. J Immunol Methods. 1987 Aug 24;102(1):127–141. doi: 10.1016/s0022-1759(87)80018-2. [DOI] [PubMed] [Google Scholar]
  30. West W. H., Tauer K. W., Yannelli J. R., Marshall G. D., Orr D. W., Thurman G. B., Oldham R. K. Constant-infusion recombinant interleukin-2 in adoptive immunotherapy of advanced cancer. N Engl J Med. 1987 Apr 9;316(15):898–905. doi: 10.1056/NEJM198704093161502. [DOI] [PubMed] [Google Scholar]
  31. Zaloom Y., Walsh L. P., McCulloch P., Gallagher G. Enhancement of a delayed hypersensitivity reaction to a contact allergen, by the systemic administration of interleukin-2. Immunology. 1991 Apr;72(4):584–587. [PMC free article] [PubMed] [Google Scholar]

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