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The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 Sep;51(9):2435–2449. doi: 10.1172/JCI107057

Lymphotoxin formation by lymphocytes and muscle in polymyositis

Robert L Johnson 1,2, Chester W Fink 1,2, Morris Ziff 1,2
PMCID: PMC292412  PMID: 4639026

Abstract

Muscle pieces from 11 patients with dermatomyositis or polymyositis were incubated with autologous peripheral blood lymphocytes and the supernates examined for the production of lymphotoxin, a mediator of delayed hypersensitivity, using human fetal muscle monolayers as the target cell. In the case of all 10 active patients, production of lymphotoxin was demonstrated. This mediator was also demonstrated when muscle alone was incubated from two patients with extensive cellular infiltration. Lymphotoxic activity was not found in supernates obtained by incubation of muscle from nine control subjects with their autologous peripheral blood lymphocytes.

Addition of methyl prednisolone to active cultures inhibited the action of lymphotoxin on the muscle monolayers. Lymphotoxin was not demonstrated when breast tumor tissue from a patient with dermatomyositis was incubated with autologous lymphocytes. The lymphotoxic agent in the active supernates had similar chromatographic properties to those of a sample of purified lymphotoxin. These findings suggest that muscle injury in polymyositis is a result of a cellular immune response to an antigen present in involved muscle tissue.

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Selected References

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  1. BARWICK D. D., WALTON J. N. POLYMYOSITIS. Am J Med. 1963 Nov;35:646–660. doi: 10.1016/0002-9343(63)90136-0. [DOI] [PubMed] [Google Scholar]
  2. Bach F. H., Voynow N. K. One-way stimulation in mixed leukocyte cultures. Science. 1966 Jul 29;153(3735):545–547. doi: 10.1126/science.153.3735.545. [DOI] [PubMed] [Google Scholar]
  3. Bubeník J., Perlmann P., Hasek M. Induction of cytotoxicity of lymphocytes from tolerant donors by antibodies to target cell alloantigens. Transplantation. 1970 Oct;10(4):290–296. [PubMed] [Google Scholar]
  4. Burnham T. K., Fine G., Neblett T. R. The immunofluorescent tumor imprint technique. II. The frequency of antinuclear factors in connective tissue diseases and dermatoses. Ann Intern Med. 1966 Jul;65(1):9–19. doi: 10.7326/0003-4819-65-1-9. [DOI] [PubMed] [Google Scholar]
  5. CASPARY E. A., GUBBAY S. S., STERN G. M. CIRCULATING ANTIBODIES IN POLYMYOSITIS AND OTHER MUSCLE-WASTING DISORDERS. Lancet. 1964 Oct 31;2(7366):941–941. doi: 10.1016/s0140-6736(64)90868-2. [DOI] [PubMed] [Google Scholar]
  6. CURTIS A. C., HECKAMAN J. H., WHEELER A. H. Study of the autoimmune reaction in dermatomyositis. JAMA. 1961 Nov 11;178:571–573. doi: 10.1001/jama.1961.73040450012007. [DOI] [PubMed] [Google Scholar]
  7. Chou S. M., Gutmann L. Picornavirus-like crystals in subacute polymyositis. Neurology. 1970 Mar;20(3):205–213. doi: 10.1212/wnl.20.3.205. [DOI] [PubMed] [Google Scholar]
  8. Chou S. M. Myxovirus-like structures and accompanying nuclear changes in chronic polymyositis. Arch Pathol. 1968 Dec;86(6):649–658. [PubMed] [Google Scholar]
  9. Chou S. M. Myxovirus-like structures in a case of human chronic polymyositis. Science. 1967 Dec 15;158(3807):1453–1455. doi: 10.1126/science.158.3807.1453. [DOI] [PubMed] [Google Scholar]
  10. Currie S. Destruction of muscle cultures by lymphocytes from cases of polymyositis. Acta Neuropathol. 1970;15(1):11–19. doi: 10.1007/BF00690685. [DOI] [PubMed] [Google Scholar]
  11. Currie S., Saunders M., Knowles M., Brown A. E. Immunological aspects of polymyositis. The in vitro activity of lymphocytes on incubation with muscle antigen and with muscle cultures. Q J Med. 1971 Jan;40(157):63–84. [PubMed] [Google Scholar]
  12. Dawkins R. L. Experimental myositis associated with hypersensitivity to muscle. J Pathol Bacteriol. 1965 Oct;90(2):619–625. doi: 10.1002/path.1700900231. [DOI] [PubMed] [Google Scholar]
  13. GLASER G. H. Polymyositis in the collagen diseases. Int J Neurol. 1960 Sep;1:319–328. [PubMed] [Google Scholar]
  14. GRACE J. T., Jr, DAO T. L. Dermatomyositis in cancer: a possible etiological mechanism. Cancer. 1959 Jul-Aug;12(4):648–650. doi: 10.1002/1097-0142(195907/08)12:4<648::aid-cncr2820120404>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  15. Gifford G. E., Tibor A., Peavy D. L. Interferon production in mixed lymphocyte cell cultures. Infect Immun. 1971 Jan;3(1):164–166. doi: 10.1128/iai.3.1.164-166.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Godal T., Rees R. J., Lamvik J. O. Lymphocyte-mediated modification of blood-derived macrophage function in vitro; inhibition of growth of intracellular mycobacteria with lymphokines. Clin Exp Immunol. 1971 Apr;8(4):625–637. [PMC free article] [PubMed] [Google Scholar]
  17. Granger G. A., Kolb W. P. Lymphocyte in vitro cytotoxicity: mechanisms of immune and non-immune small lymphocyte mediated target L cell destruction. J Immunol. 1968 Jul;101(1):111–120. [PubMed] [Google Scholar]
  18. Granger G. A., Moore G. E., White J. G., Matzinger P., Sundsmo J. S., Shupe S., Kolb W. P., Kramer J., Glade P. R. Production of lymphotoxin and migration inhibitory factor by established human lymphocytic cell lines. J Immunol. 1970 Jun;104(6):1476–1485. [PubMed] [Google Scholar]
  19. Granger G. A., Shacks S. J., Williams T. W., Kolb W. P. Lymphocyte in vitro cytotoxicity: specific release of lymphotoxin-like materials from tuberculin-sensitive lymphoid cells. Nature. 1969 Mar 22;221(5186):1155–1157. doi: 10.1038/2211155a0. [DOI] [PubMed] [Google Scholar]
  20. Hashimoto K., Robison L., Velayos E., Niizuma K. Dermatomyositis. Electron microscopic, immunologic, and tissue culture studies of paramyxovirus-like inclusions. Arch Dermatol. 1971 Feb;103(2):120–135. doi: 10.1001/archderm.103.2.120. [DOI] [PubMed] [Google Scholar]
  21. Horwitz D. A., Stastny P., Ziff M. Circulating deoxyribonucleic acid--synthesizing mononuclear leukocytes. I. Increased numbers of proliferating mononuclear leukocytes in inflammatory disease. J Lab Clin Med. 1970 Sep;76(3):391–402. [PubMed] [Google Scholar]
  22. Kakulas B. A. Destruction of differentiated muscle cultures by sensitised lymphoid cells. J Pathol Bacteriol. 1966 Apr;91(2):495–503. doi: 10.1002/path.1700910225. [DOI] [PubMed] [Google Scholar]
  23. Kakulas B. A. In vitro destruction of skeletal muscle by sensitized cells. Nature. 1966 Jun 11;210(5041):1115–1118. doi: 10.1038/2101115a0. [DOI] [PubMed] [Google Scholar]
  24. Kolb W. P., Granger G. A. Lymphocyte in vitro cytotoxicity: characterization of human lymphotoxin. Proc Natl Acad Sci U S A. 1968 Dec;61(4):1250–1255. doi: 10.1073/pnas.61.4.1250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Koren H. S., Ferber E., Fischer H. Changes in phospholipid metabolism of a tumor target cell during a cell-mediated cytotoxic reaction. Biochim Biophys Acta. 1971 May 4;231(3):520–526. doi: 10.1016/0005-2760(71)90120-2. [DOI] [PubMed] [Google Scholar]
  26. MacLennan I. C., Harding B. The role of immunoglobulins in lymphocyte-mediated cell damage, in vitro. II. The mechanism of target cell damage by lymphoid cells from immunized rats. Immunology. 1970 Mar;18(3):405–412. [PMC free article] [PubMed] [Google Scholar]
  27. MacLennan I. C., Loewi G., Harding B. The role of immunoglobulins in lymphocyte-mediated cell damage, in vitro. I. Comparison of the effects of target cell specific antibody and normal serum factors on cellular damage by immune and non-immune lymphocytes. Immunology. 1970 Mar;18(3):397–404. [PMC free article] [PubMed] [Google Scholar]
  28. Mastaglia F. L., Currie S. Immunological and ultrastructural observations on the role of lymphoid cells in the pathogenesis of polymyositis. Acta Neuropathol. 1971;18(1):1–16. doi: 10.1007/BF00684472. [DOI] [PubMed] [Google Scholar]
  29. Mastaglia F. L., Walton J. N. Coxsackie virus-like particles in skeletal muscle from a case of polymyositis. J Neurol Sci. 1970 Dec;11(6):593–599. doi: 10.1016/0022-510x(70)90109-7. [DOI] [PubMed] [Google Scholar]
  30. Morgan G., Peter J. B., Newbould B. B. Experimental allergic myositis in rats. Arthritis Rheum. 1971 Sep-Oct;14(5):599–609. doi: 10.1002/art.1780140507. [DOI] [PubMed] [Google Scholar]
  31. Norton W. L., Velayos E., Robison L. Endothelial inclusions in dermatomyositis. Ann Rheum Dis. 1970 Jan;29(1):67–72. doi: 10.1136/ard.29.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. PEARSON C. M. Development of arthritis, periarthritis and periostitis in rats given adjuvants. Proc Soc Exp Biol Med. 1956 Jan;91(1):95–101. doi: 10.3181/00379727-91-22179. [DOI] [PubMed] [Google Scholar]
  33. PEARSON C. M. Polymyositis; clinical forms, diagnosis and therapy. Postgrad Med. 1962 May;31:450–458. doi: 10.1080/00325481.1962.11694645. [DOI] [PubMed] [Google Scholar]
  34. PEARSON C. M. Rheumatic manifestations of polymyositis and dermatomyositis. Arthritis Rheum. 1959 Apr;2(2):127–143. doi: 10.1002/1529-0131(195904)2:2<127::aid-art1780020205>3.0.co;2-m. [DOI] [PubMed] [Google Scholar]
  35. Perlmann P., Perlmann H. Contactual lysis of antibody-coated chicken erythrocytes by purified lymphocytes. Cell Immunol. 1970 Sep;1(3):300–315. doi: 10.1016/0008-8749(70)90051-1. [DOI] [PubMed] [Google Scholar]
  36. Peter J. B. Cytotoxin(s) produced by human lymphocytes: inhibition by anti-inflammatory steroids and anti-malarial drugs. Cell Immunol. 1971 Apr;2(2):199–202. doi: 10.1016/0008-8749(71)90038-4. [DOI] [PubMed] [Google Scholar]
  37. Prunieras M., Grupper C., Durepaire R., Bourgeois-Spinasse J., Edelson Y. Inclusions dans la dermatomyosite aiguë et chronique. A propos de 4 cas. Presse Med. 1971 Jun 26;79(32):1463–1465. [PubMed] [Google Scholar]
  38. Rose A. L., Walton J. N. Polymyositis: a survey of 89 cases with particular reference to treatment and prognosis. Brain. 1966 Dec;89(4):747–768. doi: 10.1093/brain/89.4.747. [DOI] [PubMed] [Google Scholar]
  39. Saunders M., Knowles M., Currie S. Lymphocyte stimulation with muscle homogenate in polymyositis and other muscle-wasting disorders. J Neurol Neurosurg Psychiatry. 1969 Dec;32(6):569–571. doi: 10.1136/jnnp.32.6.569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Stern G. M., Rose A. L., Jacobs K. Circulating antibodies in polymyositis. J Neurol Sci. 1967 Jul-Aug;5(1):181–183. doi: 10.1016/0022-510x(67)90015-9. [DOI] [PubMed] [Google Scholar]
  41. Whitaker J. N., Engel W. K. Vascular deposits of immunoglobulin and complement in idiopathic inflammatory myopathy. N Engl J Med. 1972 Feb 17;286(7):333–338. doi: 10.1056/NEJM197202172860701. [DOI] [PubMed] [Google Scholar]
  42. Williams T. W., Granger G. A. Lymphocyte in vitro cytotoxicity: mechanism of lymphotoxin-induced target cell destruction. J Immunol. 1969 Apr;102(4):911–918. [PubMed] [Google Scholar]
  43. ZIFF M. The agglutination reaction in rheumatoid arthritis. J Chronic Dis. 1957 Jun;5(6):644–667. doi: 10.1016/0021-9681(57)90074-7. [DOI] [PubMed] [Google Scholar]

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