Skip to main content
Elsevier - PMC COVID-19 Collection logoLink to Elsevier - PMC COVID-19 Collection
. 2002 Nov 13;23(1):1–10. doi: 10.1016/0165-5728(89)90065-9

Virus-specific and autoreactive T cell lines isolated from cerebrospinal fluid of a patient with chronic rubella panencephalitis

Roland Martin 1,, Peter Marquardt 1, Siobhan O'Shea 2, Martin Borkenstein 3, Hans W Kreth 1,
PMCID: PMC7119901  PMID: 2470776

Abstract

Using a recently described technique for expanding of human T lymphocyte populations from cerebrospinal fluid (CSF), we investigated the local cellular immune response in a patient with chronic rubella panencephalitis. A total of 328 T cell lines (TCLs) was established by seeding CSF cells at limitin dilution into histoplates in the presence of irradiated feeder cells and phytohemagglutinin (PHA)-containing conditioned medium. 80% of TCLs expressed the CD4+ CD8, 5% the CD4 CD8+ phenotype and 15% of TCLs contained different proportions of CD4+ and CD8+ cells. Of 191 TCLs analyzed, 85 were cytotoxic, as shown by their lectin-dependent cytotoxicity against allogeneic uninfected target cells. Eight of them demonstrated specificity for the autologous, rubella virus-infected target cells. When testes for antigen-specific proliferative activity, 26 TCLs responded to rubella antigen, 16 TCLs reacted to myelin basic protein (MBP), four TCLs to proteolipid protein (PLP), four to galactocerebrosides and two to actin. Fourteen out of 16 MBP-specific TCLs also responded, to a minor degree, to rubella antigen and/or actin. The results showed that the persisting rubella infection had given rise to autoreactive T cells. Virus-induced autoreactivity to brain antigens may be an important pathogenic mechanism in other chronic inflammatory disorders of the CNS.

Keywords: Rubella panencephalitis, Cerebrospinal fluid, T cell line, Autoimmunity, Neuroantigen

Footnotes

This work was supported by Grant Kr 376/10-2 from the Deutsche Forschungsgemeinschaft, and by Grant 105/84 from the Hertie Foundation, F.R.G.

References

  1. Al-Nakib W., Best J.M., Banatvala J.E. Detection of rubella-specific IgG and IgA and nasopharyngeal IgA responses using a radioactive single immunodiffusion technique. Clin. Exp. Immunol. 1975;22:293–301. [PMC free article] [PubMed] [Google Scholar]
  2. Banik N.L., Davison A.N. Isolation of purified basic protein from human brain. J. Neurochem. 1973;21:489–494. doi: 10.1111/j.1471-4159.1973.tb05994.x. [DOI] [PubMed] [Google Scholar]
  3. Bellamy A., Davison A.N., Feldman M. Derivation of ganglioside-specific T cell lines of suppressor or helper phenotype from cerebrospinal fluid of multiple sclerosis patients. J. Neuroimmunol. 1986;12:107–120. doi: 10.1016/0165-5728(86)90024-x. [DOI] [PubMed] [Google Scholar]
  4. Bottazzo G.F., Pujol-Borell R., Hanafusa T. Role of aberrant HLA-DR expression and antigen presentation in induction of endocrine autoimmunity. Lancet. 1983;ii:1115–1118. doi: 10.1016/s0140-6736(83)90629-3. [DOI] [PubMed] [Google Scholar]
  5. Cremer N.E., Oshiro L.S., Weil M.L., Lennette E.H., Itabashi H.H., Carney L. Isolation of rubella virus from brain in chronic progressive panencephalitis. J. Gen. Virol. 1975;29:143–153. doi: 10.1099/0022-1317-29-2-143. [DOI] [PubMed] [Google Scholar]
  6. Dales S., Fujinami R.S., Oldstone M.B.A. Infection with vaccinia favors the selection of hybridomas synthesizing autoantibodies against intermediate filaments, one of them cross-reacting with the virus hemagglutinin. J. Immunol. 1983;131:1546–1553. [PubMed] [Google Scholar]
  7. Fleischer B., Kreth H.W. Clonal analysis of HLA-restricted virus-specific cytotoxic T lymphocytes from cerebrospinal fluid in mumps meningitis. J. Immunol. 1983;130:2187–2190. [PubMed] [Google Scholar]
  8. Fleischer B., Kreth H.W. Clonal expansion and functional analysis of virus-specific T lymphocytes from cerebrospinal fluid in measles encephalitis. Hum. Immunol. 1983;7:239–248. doi: 10.1016/0198-8859(83)90061-7. [DOI] [PubMed] [Google Scholar]
  9. Fleischer B., Wagner H. Significance of T4 or T8 phenotype of human cytotoxic T-lymphocyte clones. Curr. Top. Microbiol. Immunol. 1986;126:101–109. doi: 10.1007/978-3-642-71152-7_13. [DOI] [PubMed] [Google Scholar]
  10. Fleischer B., Marquardt P., Poser S., Kreth H.W. Phenotypic markers and functional characteristics of T lymphocyte clones from cerebrospinal fluid in multiple sclerosis. J. Neuroimmunol. 1984;7:151–162. doi: 10.1016/s0165-5728(84)80015-6. [DOI] [PubMed] [Google Scholar]
  11. Fujinami R.S., Oldstone M.B.A., Wroblenwska Z., Frankel M.E., Koprowski H. Vol. 80. 1983. Molecular mimicry in virus infection: cross-reaction of measles virus phosphoprotein or of herpes simplex virus protein with human intermediate filaments; pp. 2346–2350. (Proc. Natl. Acad. Sci. U.S.A.). [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hafler D.A., Buchsbaum M., Johnson D., Weiner H.L. Phenotypic and functional analysis of T cells cloned directly from the blood and cerebrospinal fluid of patients with multiple sclerosis. Ann. Neurol. 1985;18:451–458. doi: 10.1002/ana.410180407. [DOI] [PubMed] [Google Scholar]
  13. Jacobson S., Richert J.R., Biddison W.E., Satinsky A., Hartzman R.J., McFarland H. Measles virus-specific T4+ human cytotoxic T cell clones are restricted by class II HLA antigens. J. Immunol. 1984;133:754–757. [PubMed] [Google Scholar]
  14. Jahnke U., Fischer E.H., Alvord E.C. Sequence homology between certain viral proteins and proteins related to encephalomyelitis and neuritis. Science. 1985;229:282–284. doi: 10.1126/science.2409602. [DOI] [PubMed] [Google Scholar]
  15. Kretch H.W., Kress L., Kress H.G., Ott H.F., Eckert G. Demonstration of primary cytotoxic T cells in venous blood and cerebrospinal fluid of children with mumps meningitis. J. Immunol. 1982;128:2411–2415. [PubMed] [Google Scholar]
  16. Lebon P., Lyon G. Non-congenital rubella encephalitis. Lancet. 1974;ii:468. doi: 10.1016/s0140-6736(74)91853-4. (letter) [DOI] [PubMed] [Google Scholar]
  17. Lotze M.T., Rosenberg S.A. The preparation of lectin-free T cell growth factor and an analysis of its activity. J. Immunol. 1981;126:2215–2219. [PubMed] [Google Scholar]
  18. Massa P.T., Dörries R., ter Meulen V. Viral particles induce Ia antigen expression on astrocytes. Nature. 1986;320:543–546. doi: 10.1038/320543a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Rodriguez M., Pease L.R., David C.S. Immunemediated injury of virus-infected oligodendrocytes. Immunol. Today. 1986;7:359–363. doi: 10.1016/0167-5699(86)90025-3. [DOI] [PubMed] [Google Scholar]
  20. Sheshberadaran H., Norrby E. Three monoclonal antibodies against measles virus F protein cross-react with cellular stress proteins. J. Virol. 1984;52:995–999. doi: 10.1128/jvi.52.3.995-999.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stoffel W., Hillen H., Schröder W., Deutzmann R. The primary structure of bovine brain lipophyllin (proteolipid) Hoppe-Seyler's Zbl. Physiol. Chem. 1983;364:1455–1466. doi: 10.1515/bchm2.1983.364.2.1455. [DOI] [PubMed] [Google Scholar]
  22. Ter meulen V., Stephenson J.R., Kreth H.W. Subacute sclerosing panencephalitis. In: Fraenkel-Conrat H., Wagner R.R., editors. Vol. 18. Plenum; New York: 1983. (Comprehensive Virology). [Google Scholar]
  23. Townsend J.J., Baringer J.R., Wolinsky J.S., Malamud N., Mednick J.P., Panitch H.S., Scott R.A.T., Oshiro L.S., Cremer N.E. Progressive rubella panencephalitis. New Engl. J. Med. 1975;292:990–993. doi: 10.1056/NEJM197505082921902. [DOI] [PubMed] [Google Scholar]
  24. Townsend J.J., Wolinsky J.S., Baringer J.R. The neuropathology of progressive rubella panencephalitis of late onset. Brain. 1976;99:81–90. doi: 10.1093/brain/99.1.81. [DOI] [PubMed] [Google Scholar]
  25. Watanabe R., Wege H., ter Meulen V. Adoptive transfer of EAE-like lesions from rats with coronabirus-induced demyelinating encephalomyelitis. Nature. 1983;305:150–153. doi: 10.1038/305150a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Waxham M.N., Wolinsky J.S. Rubella virus and its effects on the central nervous system. Neurol. Clin. 1984;2:367–385. [PubMed] [Google Scholar]
  27. Webb H.E., Fazakerley J.K. Can viral envelope glycolipids produce auto-immunity, with reference to the CNS and multiple sclerosis? Neuropathol. Appl. Neurobiol. 1983;10:1–10. doi: 10.1111/j.1365-2990.1984.tb00335.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weil M.L., Itabashi H., Cremer N.E., Oshiro L.S., Lennette E.H., Carnay L. Chronic progressive panencephalitis due to rubella virus simulating subacute sclerosing panencephalitis. New Engl. J. Med. 1975;292:994–998. doi: 10.1056/NEJM197505082921903. [DOI] [PubMed] [Google Scholar]
  29. Wolinsky J.S., Berg B.P., Maitland C.J. Progressive rubella panencephalitis. Arch. Neurol. 1976;33:722–723. doi: 10.1001/archneur.1976.00500100056016. [DOI] [PubMed] [Google Scholar]
  30. Wolinsky J.S., Dau P.C., Bumivici-Klein E., Mednick J., Berg B.O., Lang P.B., Cooper L.Z. Progressive rubella panencephalitis: immunovirological studies and results of isoprinosine therapy. Clin. Exp. Immunol. 1979;35:397–404. [PMC free article] [PubMed] [Google Scholar]
  31. Yasukawa M., Zarling J.M. Human cytotoxic T lymphocytes clones directed against herpes simplex virus-infected cells. I. Lysis restricted by HLA class II MB or DR antigen. J. Immunol. 1984;133:422–428. [PubMed] [Google Scholar]

Articles from Journal of Neuroimmunology are provided here courtesy of Elsevier

RESOURCES