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. 1986 Sep 1;164(3):814–825. doi: 10.1084/jem.164.3.814

Dissection of the lymphokine-activated killer phenomenon. Relative contribution of peripheral blood natural killer cells and T lymphocytes to cytolysis

PMCID: PMC2188384  PMID: 3489062

Abstract

In vitro culture of human peripheral blood lymphocytes in IL-2 results in the generation of cytotoxic cells that can lyse fresh and cultured solid tumor cells, as well as hematopoietic tumor cell lines, without deliberate immunization or MHC restriction. This has been referred to as the lymphokine activated killer (LAK) phenomenon. Here, we show that the majority of this activity is mediated by NK cells that express the Leu-19 (NKH-1) antigen, but do not express CD3. The precursor of this effector population also expressed the phenotype CD3-, Leu-19+. Peripheral blood CD3+ T lymphocytes contributed little to the LAK phenomenon, although low levels of non-MHC restricted cytotoxicity against hematopoietic tumor cell targets were mediated by a subset of CD3+ T lymphocytes that coexpressed the Leu-19 antigen. These studies clearly indicated that the LAK phenomenon is not mediated by a unique LAK cell, but is mediated mainly by IL-2-activated peripheral blood NK cells.

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Selected References

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  1. 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]
  2. 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]
  3. 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]
  4. Hercend T., Griffin J. D., Bensussan A., Schmidt R. E., Edson M. A., Brennan A., Murray C., Daley J. F., Schlossman S. F., Ritz J. Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest. 1985 Mar;75(3):932–943. doi: 10.1172/JCI111794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Itoh K., Tilden A. B., Kumagai K., Balch C. M. Leu-11+ lymphocytes with natural killer (NK) activity are precursors of recombinant interleukin 2 (rIL 2)-induced activated killer (AK) cells. J Immunol. 1985 Feb;134(2):802–807. [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Lanier L. L., Le A. M., Civin C. I., Loken M. R., Phillips J. H. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986 Jun 15;136(12):4480–4486. [PubMed] [Google Scholar]
  9. 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]
  10. Phillips J. H., Lanier L. L. A model for the differentiation of human natural killer cells. Studies on the in vitro activation of Leu-11+ granular lymphocytes with a natural killer-sensitive tumor cell, K562. J Exp Med. 1985 Jun 1;161(6):1464–1482. doi: 10.1084/jem.161.6.1464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Phillips J. H., Lanier L. L. Lectin-dependent and anti-CD3 induced cytotoxicity are preferentially mediated by peripheral blood cytotoxic T lymphocytes expressing Leu-7 antigen. J Immunol. 1986 Mar 1;136(5):1579–1585. [PubMed] [Google Scholar]
  12. Phillips J. H., Warner N. L., Lanier L. L. Correlation of biophysical properties and cell surface antigenic profile of Percoll gradient-separated human natural killer cells. Nat Immun Cell Growth Regul. 1983;3(2):73–86. [PubMed] [Google Scholar]
  13. Reinherz E. L., Hussey R. E., Schlossman S. F. A monoclonal antibody blocking human T cell function. Eur J Immunol. 1980 Oct;10(10):758–762. doi: 10.1002/eji.1830101006. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Spits H., Yssel H., Leeuwenberg J., De Vries J. E. Antigen-specific cytotoxic T cell and antigen-specific proliferating T cell clones can be induced to cytolytic activity by monoclonal antibodies against T3. Eur J Immunol. 1985 Jan;15(1):88–91. doi: 10.1002/eji.1830150117. [DOI] [PubMed] [Google Scholar]
  16. Toribio M. L., De Landázuri M. O., López-Botet M. Induction of natural killer-like cytotoxicity in cultured human thymocytes. Eur J Immunol. 1983 Dec;13(12):964–969. doi: 10.1002/eji.1830131203. [DOI] [PubMed] [Google Scholar]
  17. Trinchieri G., Matsumoto-Kobayashi M., Clark S. C., Seehra J., London L., Perussia B. Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med. 1984 Oct 1;160(4):1147–1169. doi: 10.1084/jem.160.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]

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