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. 1987 May;50(5):532–537. doi: 10.1136/jnnp.50.5.532

T lymphocyte-derived demyelinating activity in multiple sclerosis patients in relapse.

K Selmaj, R Alam, G D Perkin, F C Rose
PMCID: PMC1031963  PMID: 3495638

Abstract

Supernatants of cultured T lymphocytes of multiple sclerosis patients were tested for a demyelinating activity in rat cerebellum explant cultures. Supernatants of unstimulated T lymphocytes in seven out of 10 multiple sclerosis patients in relapse produced demyelination when checked by phase contrast microscopy. Supernatants of unstimulated T lymphocytes from healthy subjects did not produce demyelination, but when T cells were stimulated by phytohaemagglutinin (PHA), 50% of tested supernatants produced demyelination, which was, however, never as advanced as in multiple sclerosis supernatant treated cerebellum cultures. The demyelinating activity proved to be heat labile. Gel filtration study revealed two fractions of the demyelinating activity 12.5-29.0 kD and 43.0-66.0 kD. The results suggest that lymphokines can be directly involved in the pathogenesis of demyelination in multiple sclerosis.

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Selected References

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

  1. Al-Ibrahim M. S., Chandra R., Kishore R., Valentine F. T., Lawrence H. S. A micromethod for evaluating the phagocytic activity of human macrophages by ingestion of radio-labelled polystyrene particles. J Immunol Methods. 1976 Mar;10(2-3):207–218. doi: 10.1016/0022-1759(76)90172-1. [DOI] [PubMed] [Google Scholar]
  2. BORNSTEIN M. B., MURRAY M. R. Serial observations on patterns of growth, myelin formation, maintenance and degeneration in cultures of new-born rat and kitten cerebellum. J Biophys Biochem Cytol. 1958 Sep 25;4(5):499–504. doi: 10.1083/jcb.4.5.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brosnan C. F., Stoner G. L., Bloom B. R., Wisniewski H. M. Studies on demyelination by activated lymphocytes in the rabbit eye. II. Antibody-dependent cell-mediated demyelination. J Immunol. 1977 Jun;118(6):2103–2110. [PubMed] [Google Scholar]
  4. Bøyum A. Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol. 1976 Jun;Suppl 5:9–15. [PubMed] [Google Scholar]
  5. Cammer W., Bloom B. R., Norton W. T., Gordon S. Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages: a possible mechanism of inflammatory demyelination. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1554–1558. doi: 10.1073/pnas.75.3.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Coleman D. L., Culver K. E., Ryan J. L. Enhancement of macrophage immune and nonimmune receptor-mediated phagocytosis by a low molecular weight soluble factor from resident thymocytes. J Immunol. 1984 Dec;133(6):3121–3127. [PubMed] [Google Scholar]
  7. Ellison G. W., Waksman B. H., Ruddle N. H. Experimental autoallergic encephalomyelitis and cellular hypersensitivity in vitro. Neurology. 1971 Aug;21(8):778–782. doi: 10.1212/wnl.21.8.778. [DOI] [PubMed] [Google Scholar]
  8. Esiri M. M. Multiple sclerosis: a quantitative and qualitative study of immunoglobulin-containing cells in the central nervous system. Neuropathol Appl Neurobiol. 1980 Jan-Feb;6(1):9–21. doi: 10.1111/j.1365-2990.1980.tb00199.x. [DOI] [PubMed] [Google Scholar]
  9. Gemsa D., Kubelka C., Debatin K. M., Krammer P. H. Activation of macrophages by lymphokines from T-cell clones: evidence for different macrophage-activating factors. Mol Immunol. 1984 Dec;21(12):1267–1276. doi: 10.1016/0161-5890(84)90020-8. [DOI] [PubMed] [Google Scholar]
  10. Lumsden C. E. The immunogenesis of the multiple sclerosis plaque. Brain Res. 1971 May 21;28(3):365–390. doi: 10.1016/0006-8993(71)90052-7. [DOI] [PubMed] [Google Scholar]
  11. Mahowald M. L., Handwerger B. S., Capertone E. M., Jr, Douglas S. D. A comparative study of procedures for sheep erythrocyte-human-T-lymphocyte rosette formation. J Immunol Methods. 1977;15(3):239–245. doi: 10.1016/0022-1759(77)90061-8. [DOI] [PubMed] [Google Scholar]
  12. McDonald W. I., Halliday A. M. Diagnosis and classification of multiple sclerosis. Br Med Bull. 1977 Jan;33(1):4–9. [PubMed] [Google Scholar]
  13. Merrill J. E., Kutsunai S., Mohlstrom C., Hofman F., Groopman J., Golde D. W. Proliferation of astroglia and oligodendroglia in response to human T cell-derived factors. Science. 1984 Jun 29;224(4656):1428–1430. doi: 10.1126/science.6610212. [DOI] [PubMed] [Google Scholar]
  14. Okamoto M., Mayer M. M. Studies on the mechanism of action of guinea pig lymphotoxin. II. Increase of calcium uptake rate in LT-damaged target cells. J Immunol. 1978 Jan;120(1):279–285. [PubMed] [Google Scholar]
  15. Prineas J. Pathology of the early lesion in multiple sclerosis. Hum Pathol. 1975 Sep;6(5):531–554. doi: 10.1016/s0046-8177(75)80040-2. [DOI] [PubMed] [Google Scholar]
  16. Raine C. S. Biology of disease. Analysis of autoimmune demyelination: its impact upon multiple sclerosis. Lab Invest. 1984 Jun;50(6):608–635. [PubMed] [Google Scholar]
  17. Ruddle N. H., Waksman B. H. Cytotoxicity mediated by soluble antigen and lymphocytes in delayed hypersensitivity. 3. Analysis of mechanism. J Exp Med. 1968 Dec 1;128(6):1267–1279. doi: 10.1084/jem.128.6.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Traugott U., Reinherz E. L., Raine C. S. Multiple sclerosis. Distribution of T cells, T cell subsets and Ia-positive macrophages in lesions of different ages. J Neuroimmunol. 1983 Jun;4(3):201–221. doi: 10.1016/0165-5728(83)90036-x. [DOI] [PubMed] [Google Scholar]
  19. Traugott U., Reinherz E. L., Raine C. S. Multiple sclerosis: distribution of T cell subsets within active chronic lesions. Science. 1983 Jan 21;219(4582):308–310. doi: 10.1126/science.6217550. [DOI] [PubMed] [Google Scholar]
  20. Waksman B. H., Reynolds W. E. Multiple sclerosis as a disease of immune regulation. Proc Soc Exp Biol Med. 1984 Mar;175(3):282–294. doi: 10.3181/00379727-175-41798. [DOI] [PubMed] [Google Scholar]

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