Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1974 Apr 1;139(4):902–924. doi: 10.1084/jem.139.4.902

DEMONSTRATION OF A BLOCKING FACTOR IN THE PLASMA AND SPINAL FLUID OF PATIENTS WITH SUBACUTE SCLEROSING PANENCEPHALITIS

I. PARTIAL CHARACTERIZATION

Aftab Ahmed 1, Douglas M Strong 1, Kenneth W Sell 1, Gary B Thurman 1, Richard C Knudsen 1, Richard Wistar Jr 1, William R Grace 1
PMCID: PMC2139563  PMID: 4593239

Abstract

Conflicting reports on the immune responsiveness of patients with subacute sclerosing panencephalitis (SSPE) have been reported. This report shows that the leucocytes from four SSPE patients exhibited strong sensitivity to both measles and SSPE virus preparations as measured by the macrophage migration inhibition test, mixed lymphocyte virus infected cell culture test, and the lymphotoxin assay. Earlier suggestions that a factor may be operating to suppress cellular reactivity are confirmed by the demonstration that the response of lymphocytes from SSPE patients could be blocked by the addition of SSPE spinal fluid or plasma. It was determined that the blocking factor was stable at –20°C, heat labile at 56°C for 30 minutes, trypsin and neuraminadase sensitive, and had a mol wt greater than 150,000 as determined by Sephadex G-200 gel chromatography. The blocking factor appeared to be specific for SSPE virus and did not block the response of lymphocytes to nonspecific mitogenic agents and other viral and bacterial agents.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Allen J., Oppenheim J., Brody J. A., Miller J. Labile inhibitor of lymphocyte transformation in plasma from a patient and subacute sclerosing panencephalitis. Infect Immun. 1973 Jul;8(1):80–82. doi: 10.1128/iai.8.1.80-82.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allison A. C., Beveridge W. I., Cockburn W. C., East J., Goodman H. C., Koprowksi H., Lambert P. H., van Lochem J. J., Miescher P. A., Mimms C. A. Virus-associated immunopathology: animal models and implications for human disease. 2. Cell-mediated immunity, autoimmune diseases, genetics, and implications for clinical research. Bull World Health Organ. 1972;47(2):265–274. [PMC free article] [PubMed] [Google Scholar]
  3. BAER H., CHAPARAS S. D. TUBERCULIN REACTIVITY OF A CARBOHYDRATE COMPONENT OF UNHEATED BCG CULTURE FILTRATE. Science. 1964 Oct 9;146(3641):245–247. doi: 10.1126/science.146.3641.245. [DOI] [PubMed] [Google Scholar]
  4. Barbanti-Brodano G., Oyanagi S., Katz M., Koprowski H. Presence of 2 different viral agents in brain cells of patients with subacute sclerosing panencephalitis. Proc Soc Exp Biol Med. 1970 May;134(1):230–236. doi: 10.3181/00379727-134-34765. [DOI] [PubMed] [Google Scholar]
  5. Connolly J. H., Allen I. V., Hurwitz L. J., Millar J. H. Measles-virus antibody and antigen in subacute sclerosing panencephalitis. Lancet. 1967 Mar 11;1(7489):542–544. doi: 10.1016/s0140-6736(67)92117-4. [DOI] [PubMed] [Google Scholar]
  6. Cooperband S. R., Bondevik H., Schmid K., Mannick J. A. Transformation of human lymphocytes: inhibition by homologous alpha globulin. Science. 1968 Mar 15;159(3820):1243–1244. doi: 10.1126/science.159.3820.1243. [DOI] [PubMed] [Google Scholar]
  7. Dayan A. D. Encephalitis due to simultaneous infection by herpes simplex and measles viruses. J Neurol Sci. 1971 Nov;14(3):315–323. doi: 10.1016/0022-510x(71)90220-6. [DOI] [PubMed] [Google Scholar]
  8. Dayan A. D., Stokes M. I. Immune complexes and visceral deposits of measles antigens in subacute sclerosing panencephalitis. Br Med J. 1972 May 13;2(5810):374–376. doi: 10.1136/bmj.2.5810.374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dayan A. D., Stokes M. I. Immunofluorescent detection of measles-virus antigens in cerebrospinal-fluid cells in subacute sclerosing panencephalitis. Lancet. 1971 May 1;1(7705):891–892. doi: 10.1016/s0140-6736(71)92447-0. [DOI] [PubMed] [Google Scholar]
  10. Gatti R. A. Serum inhibitors of lymphocyte responses. Lancet. 1971 Jun 26;1(7713):1351–1352. doi: 10.1016/s0140-6736(71)91906-4. [DOI] [PubMed] [Google Scholar]
  11. Gerber P., Lucas S. J. In vitro stimulation of human lymphocytes by Epstein-Barr virus. Cell Immunol. 1972 Oct;5(2):318–324. doi: 10.1016/0008-8749(72)90057-3. [DOI] [PubMed] [Google Scholar]
  12. Gerson K. L., Haslam R. H. Subtle immunologic abnormalities in four boys with subacute sclerosing panencephalitis. N Engl J Med. 1971 Jul 8;285(2):78–82. doi: 10.1056/NEJM197107082850203. [DOI] [PubMed] [Google Scholar]
  13. Godfrey H. P., Baer H., Chaparas S. D. Inhibition of macrophage migration by a skin-reactive polysaccharide from BCG culture filtrates. J Immunol. 1969 Jun;102(6):1466–1473. [PubMed] [Google Scholar]
  14. 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]
  15. Hartzman R. J., Bach M. L., Bach F. H., Thurman G. B., Sell K. W. Precipitation of radioactively labeled samples: a semi-automatic multiple-sample processor. Cell Immunol. 1972 Jun;4(2):182–186. doi: 10.1016/0008-8749(72)90018-4. [DOI] [PubMed] [Google Scholar]
  16. Horta-Barbosa L., Hamilton R., Wittig B., Fuccillo D. A., Sever J. L., Vernon M. L. Subacute sclerosing panencephalitis: isolation of suppressed measles virus from lymph node biopsies. Science. 1971 Aug 27;173(3999):840–841. doi: 10.1126/science.173.3999.840. [DOI] [PubMed] [Google Scholar]
  17. Horta-Barbosa L., Krebs H., Ley A., Chen T. C., Gilkeson M. R., Sever J. L. Progressive increase in cerebrospinal fluid measles antibody levels in subacute sclerosing panencephalitis. Pediatrics. 1971 Apr;47(4):782–783. [PubMed] [Google Scholar]
  18. Jabbour J. T., Duenas D. A., Sever J. L., Krebs H. M., Horta-Barbosa L. Epidemiology of subacute sclerosing panencephalitis (SSPE). A report of the SSPE registry. JAMA. 1972 May 15;220(7):959–962. [PubMed] [Google Scholar]
  19. Jabbour J. T., Roane J. A., Sever J. L. Studies of delayed dermal hypersensitivity in patients with subacute sclerosing panencephalitis. Neurology. 1969 Oct;19(10):929–931. doi: 10.1212/wnl.19.10.929. [DOI] [PubMed] [Google Scholar]
  20. Katz M., Rorke L. B., Masland W. S., Koprowski H., Tucker S. H. Transmission of an encephalitogenic agent from brains of patients with subacute sclerosing panencephalitis to ferrets. Preliminary report. N Engl J Med. 1968 Oct 10;279(15):793–798. doi: 10.1056/NEJM196810102791503. [DOI] [PubMed] [Google Scholar]
  21. Knowles M., Hughes D., Caspary E. A., Field E. J. Lymphocyte transformation in multiple sclerosis. Inhibition of unstimulated thymidine uptake by a serum factor. Lancet. 1968 Dec 7;2(7580):1207–1209. doi: 10.1016/s0140-6736(68)91691-7. [DOI] [PubMed] [Google Scholar]
  22. Kolar O. Measles and subacute sclerosing panencephalitis. Lancet. 1968 Dec 7;2(7580):1242–1242. doi: 10.1016/s0140-6736(68)91719-4. [DOI] [PubMed] [Google Scholar]
  23. Lehrich J. R., Katz M., Rorke L. B., Barbanti-Brodano G., Koprowski H. Subacute sclerosing panencephalitis viruses: induction of experimental encephalitis in hamsters. Trans Am Neurol Assoc. 1970;95:51–56. [PubMed] [Google Scholar]
  24. McFarlin D. E., Oppenheim J. J. Impaired lymphocyte transformation in ataxia-telangiectasia in part due to a plasma inhibitory factor. J Immunol. 1969 Dec;103(6):1212–1222. [PubMed] [Google Scholar]
  25. Mizutani H., Saito S., Nihei K., Izuchi T. Cellular hypersensitivity in subacute sclerosing panencephalitis. JAMA. 1971 May 17;216(7):1201–1202. doi: 10.1001/jama.1971.03180330075025. [DOI] [PubMed] [Google Scholar]
  26. Moulias R. L., Reinert P., Goust J. M. Immunologic abnormalities in subacute sclerosing panencephalitis. N Engl J Med. 1971 Nov 4;285(19):1090–1090. [PubMed] [Google Scholar]
  27. Müller D., ter Meulen V., Katz M., Koprowski H. Cytochemical evidence for the presence of two viral agents in subacute sclerosing panencephalitis. Lab Invest. 1971 Oct;25(4):337–342. [PubMed] [Google Scholar]
  28. Phillips P. E. Immune complexes in subacute sclerosing panencephalitis. N Engl J Med. 1972 Apr 27;286(17):949–950. doi: 10.1056/NEJM197204272861715. [DOI] [PubMed] [Google Scholar]
  29. Rosenberg G. L., Farber P. A., Notkins A. L. In vitro stimulation of sensitized lymphocytes by herpes simplex virus and vaccinia virus. Proc Natl Acad Sci U S A. 1972 Mar;69(3):756–760. doi: 10.1073/pnas.69.3.756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Scheurlen P. G., Schneider W., Pappas A. Inhibition of transformation of normal lymphocytes by plasma factor from patients with Hodgkin's disease and cancer. Lancet. 1971 Dec 4;2(7736):1265–1265. doi: 10.1016/s0140-6736(71)90586-1. [DOI] [PubMed] [Google Scholar]
  31. Sell K. W., Thurman G. B., Ahmed A., Strong D. M. Plasma and spinal-fluid blocking factor in SSPE. N Engl J Med. 1973 Jan 25;288(4):215–216. doi: 10.1056/nejm197301252880418. [DOI] [PubMed] [Google Scholar]
  32. Shacks S. J., Chiller J., Granger G. A. Studies on in vitro models of cellular immunity: the role of T and B cells in the secretion of lymphotoxin. Cell Immunol. 1973 May;7(2):313–321. doi: 10.1016/0008-8749(73)90253-0. [DOI] [PubMed] [Google Scholar]
  33. Silk M. Effect of plasma from patients with carcinoma on in vitro lymphocyte transformation. Cancer. 1967 Dec;20(12):2088–2089. doi: 10.1002/1097-0142(196712)20:12<2088::aid-cncr2820201205>3.0.co;2-1. [DOI] [PubMed] [Google Scholar]
  34. Spitler L., Benjamini E., Young J. D., Kaplan H., Fudenberg H. H. Studies on the immune response to a characterized antigenic determinant of the tobacco mosaic virus protein. J Exp Med. 1970 Jan 1;131(1):133–148. doi: 10.1084/jem.131.1.133. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Strong D. M., Ahmed A. A., Thurman G. B., Sell K. W. In vitro stimulation of murine spleen cells using a microculture system and a multiple automated sample harvester. J Immunol Methods. 1973 Apr;2(3):279–291. doi: 10.1016/0022-1759(73)90054-9. [DOI] [PubMed] [Google Scholar]
  36. Thein P., Mayr A., ter Muelen V., Koprowski H., Käckell M. Y., Müller D., Meyermann R. Subacute sclerosing panencephalitis. Transmission of the virus to calves and lambs. Arch Neurol. 1972 Dec;27(6):540–548. doi: 10.1001/archneur.1972.00490180076016. [DOI] [PubMed] [Google Scholar]
  37. Thurman G. B., Ahmed A., Strong D. M., Knudsen R. C., Grace W. R., Sell K. W. Lymphocyte activation in subacute sclerosing panencephalitis virus and cytomegalovirus infections. In vitro stimulation in response to viral-infected cell lines. J Exp Med. 1973 Oct 1;138(4):839–846. doi: 10.1084/jem.138.4.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vandvik B. Immunological studies in subacute sclerosing panencephalitis. Acta Neurol Scand. 1970;46(Suppl):232–232. doi: 10.1111/j.1600-0404.1970.tb02203.x. [DOI] [PubMed] [Google Scholar]
  39. Youtananukorn V., Mantangkasombut P. Specific plasma factors blocking human maternal cell-mediated immune reaction to placental antigens. Nat New Biol. 1973 Mar 28;242(117):110–111. doi: 10.1038/newbio242110a0. [DOI] [PubMed] [Google Scholar]
  40. ter Muelen V., Enders-Ruckle G., Müller D., Joppich G. Immunhistological, microscopical and neurochemical studies on encephalitides. 3. Subacute progressive panencephalitis. Virological and immunhistological studies. Acta Neuropathol. 1969;12(3):244–259. doi: 10.1007/BF00687648. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES