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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1987 Jun;68(3):535–542.

Lymphokine-activated killer cell activity in rheumatoid arthritis.

M Jíra 1, M Malkovský 1, A M Denman 1, B Loveland 1, D Lyons 1, A G Dalgleish 1, A D Webster 1
PMCID: PMC1542760  PMID: 3498578

Abstract

The lymphokine-activated killer (LAK) cell activity in the peripheral blood of 23 patients with rheumatoid arthritis has been studied. Two control groups comprised (a) nine patients with another chronic inflammatory disease (sarcoidosis) and (b) 19 normal healthy volunteers. The LAK activity induced by human recombinant IL-2 was very similar in controls and patients with rheumatoid arthritis but was significantly decreased in patients with sarcoidosis, although the frequency of LAK-cell precursors measured using a limiting dilution assay was comparable in all three groups. The DNA synthetic response of peripheral blood mononuclear (PBM) cells to IL-2 was slightly decreased in patients with both rheumatoid arthritis and sarcoidosis as compared to controls, but this decrease was not statistically significant. Spontaneous DNA synthesis in PBM cells cultured in the absence of IL-2 was essentially identical in all three groups. We conclude on the basis of these results that the higher risk of non-Hodgkin's lymphomas in patients with rheumatoid arthritis cannot be attributed to an impairment of LAK activity. Furthermore, the doses of gamma-irradiation, which abolished the 'background' cytotoxicity of PBM cells cultured without IL-2 and also blocked effectively both spontaneous and exogenous IL-2-dependent DNA synthesis, had little effect on the generation of LAK activity. These observations are discussed in regard to the role of non-specific cytotoxic cells and the therapeutic efficacy of antiproliferative drugs in rheumatoid arthritis.

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Selected References

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

  1. Baltus J. A., Boersma J. W., Hartman A. P., Vandenbroucke J. P. The occurrence of malignancies in patients with rheumatoid arthritis treated with cyclophosphamide: a controlled retrospective follow-up. Ann Rheum Dis. 1983 Aug;42(4):368–373. doi: 10.1136/ard.42.4.368. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bubeník J., Asfahani A., Sherif M., El Ridi R., Mach O., Machácková M., Jandlová T., Símová J., Hanus M., Hradec E. Human urinary bladder carcinoma cell line (T24): immunological studies and search for oncornavirus in T24 cell population and derived clones. Neoplasma. 1978;25(5):513–522. [PubMed] [Google Scholar]
  3. Cheever M. A., Greenberg P. D., Fefer A., Gillis S. Augmentation of the anti-tumor therapeutic efficacy of long-term cultured T lymphocytes by in vivo administration of purified interleukin 2. J Exp Med. 1982 Apr 1;155(4):968–980. doi: 10.1084/jem.155.4.968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Colizzi V. In vivo and in vitro administration of interleukin 2-containing preparation reverses T-cell unresponsiveness in Mycobacterium bovis BCG-infected mice. Infect Immun. 1984 Jul;45(1):25–28. doi: 10.1128/iai.45.1.25-28.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Combe B., Pope R. M., Fischbach M., Darnell B., Baron S., Talal N. Interleukin-2 in rheumatoid arthritis: production of and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood. Clin Exp Immunol. 1985 Mar;59(3):520–528. [PMC free article] [PubMed] [Google Scholar]
  6. Depper J. M., Bluestein H. G., Zvaifler N. J. Impaired regulation of Epstein-Barr virus-induced lymphocyte proliferation in rheumatoid arthritis is due to a T cell defect. J Immunol. 1981 Nov;127(5):1899–1902. [PubMed] [Google Scholar]
  7. Domzig W., Stadler B. M., Herberman R. B. Interleukin 2 dependence of human natural killer (NK) cell activity. J Immunol. 1983 Apr;130(4):1970–1973. [PubMed] [Google Scholar]
  8. Emery P., Panayi G., Symmons D., Brown G. Mechanisms of depressed delayed-type hypersensitivity in rheumatoid arthritis: the role of protein energy malnutrition. Ann Rheum Dis. 1984 Jun;43(3):430–434. doi: 10.1136/ard.43.3.430. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gao L., Malkovský M., Webster A. D., Asherson G. L. Impaired lymphokine-activated killer-cell activity in patients with hypogammaglobulinaemia. Lancet. 1985 Aug 10;2(8450):340–340. doi: 10.1016/s0140-6736(85)90394-0. [DOI] [PubMed] [Google Scholar]
  10. Goto M., Tanimoto K., Chihara T., Horiuchi Y. Natural cell-mediated cytotoxicity in Sjögren's syndrome and rheumatoid arthritis. Arthritis Rheum. 1981 Nov;24(11):1377–1382. doi: 10.1002/art.1780241107. [DOI] [PubMed] [Google Scholar]
  11. Goto M., Zvaifler N. J. Characterization of the killer cell generated in the autologous mixed leukocyte reaction. J Exp Med. 1983 Apr 1;157(4):1309–1323. doi: 10.1084/jem.157.4.1309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goto M., Zvaifler N. J. Impaired killer cell generation in the autologous mixed leukocyte reaction by rheumatoid arthritis lymphocytes. Arthritis Rheum. 1985 Jul;28(7):731–741. doi: 10.1002/art.1780280703. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Irving W. L., Walker P. R., Lydyard P. M. Abnormal responses of rheumatoid arthritis lymphocytes to Epstein-Barr virus infection in vitro: evidence for multiple defects. Ann Rheum Dis. 1985 Jul;44(7):462–468. doi: 10.1136/ard.44.7.462. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kahan A., Kahan A., Amor B., Menkes C. J. Different defects of T cell regulation of Epstein-Barr virus-induced B cell activation in rheumatoid arthritis. Arthritis Rheum. 1985 Sep;28(9):961–970. doi: 10.1002/art.1780280902. [DOI] [PubMed] [Google Scholar]
  16. Liang S. M., Allet B., Rose K., Hirschi M., Liang C. M., Thatcher D. R. Characterization of human interleukin 2 derived from Escherichia coli. Biochem J. 1985 Jul 15;229(2):429–439. doi: 10.1042/bj2290429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Loveland B., Hunt R., Malkovský M. Autologous lymphoid cells exposed to recombinant interleukin-2 in vitro in the absence of antigen can induce the rejection of long-term tolerated skin allografts. Immunology. 1986 Sep;59(1):159–161. [PMC free article] [PubMed] [Google Scholar]
  18. Malkovsky M., Asherson G. L., Stockinger B., Watkins M. C. Nonspecific inhibitor released by T acceptor cells reduces the production of interleukin-2. Nature. 1982 Dec 16;300(5893):652–655. doi: 10.1038/300652a0. [DOI] [PubMed] [Google Scholar]
  19. Malkovský M., Doré C., Hunt R., Palmer L., Chandler P., Medawar P. B. Enhancement of specific antitumor immunity in mice fed a diet enriched in vitamin A acetate. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6322–6326. doi: 10.1073/pnas.80.20.6322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Malkovský M., Jíra M., Gao L., Loveland B., Malkovska V., Dalgleish A. G., Webster A. D. Reduced expression of interleukin-2 receptors in hypogammaglobulinaemia: a possible cause of higher cancer incidence. Lancet. 1986 Jun 21;1(8495):1442–1443. doi: 10.1016/s0140-6736(86)91586-2. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. 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]
  23. Malkovský M., Medawar P., Hunt R., Palmer L., Doré C. A diet enriched in vitamin A acetate or in vivo administration of interleukin-2 can counteract a tolerogenic stimulus. Proc R Soc Lond B Biol Sci. 1984 Feb 22;220(1221):439–445. doi: 10.1098/rspb.1984.0012. [DOI] [PubMed] [Google Scholar]
  24. Mulé J. J., Shu S., Schwarz S. L., Rosenberg S. A. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science. 1984 Sep 28;225(4669):1487–1489. doi: 10.1126/science.6332379. [DOI] [PubMed] [Google Scholar]
  25. Pope R. M., McChesney L., Talal N., Fischbach M. Characterization of the defective autologous mixed lymphocyte response in rheumatoid arthritis. Arthritis Rheum. 1984 Nov;27(11):1234–1244. doi: 10.1002/art.1780271105. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Rosenberg S. A. The adoptive immunotherapy of cancer using the transfer of activated lymphoid cells and interleukin-2. Semin Oncol. 1986 Jun;13(2):200–206. [PubMed] [Google Scholar]
  28. Silver R. M., Redelman D., Zvaifler N. J., Naides S. Studies of rheumatoid synovial fluid lymphocytes. I. Evidence for activated natural killer- (NK) like cells. J Immunol. 1982 Apr;128(4):1758–1763. [PubMed] [Google Scholar]
  29. Silver R. M., Redelman D., Zvaifler N. J. Studies of rheumatoid synovial fluid lymphocytes. II. A comparison of their behavior with blood mononuclear cells in the autologous mixed lymphocyte reaction and response to TCGF. Clin Immunol Immunopathol. 1983 Apr;27(1):15–27. doi: 10.1016/0090-1229(83)90052-1. [DOI] [PubMed] [Google Scholar]
  30. Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol. 1981 Apr;126(4):1614–1619. [PubMed] [Google Scholar]
  31. Trentham D. E., Weinblatt M. E., Austen K. F. Total lymphoid irradiation in tertiary care for rheumatoid arthritis. Ann Intern Med. 1985 Apr;102(4):544–545. doi: 10.7326/0003-4819-102-4-544. [DOI] [PubMed] [Google Scholar]

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