Brain cell lesions in Borna disease are mediated by T cells

  • T. Bilzer
  • L. Stitz
Part of the Archives of Virology book series (ARCHIVES SUPPL, volume 7)


Experimental Borna Disease (BD) in rats is characterized by severe lymphocytic encephalitis and by massive brain cell lesions finally leading to brain atrophy. Treatment of BDV-infected rats with monoclonal antibodies directed against CD4+ and CD8+ T cells could almost completely inhibit the immunopathological reactions and revealed less BDV-infected neurons and astrocytes that expressed MHC class I antigen. Brain cell lesions were minimal, and no obvious brain atrophy could be observed even late after infection. Since BDV itself is not known to exert cytopathic effects and since brain cell damage was independent of antibody titers, brain cell destruction correlates well with the intracerebral presence of CD8+ T cells and the expression of MHC class I antigens. Moreover, BDV-infected brain cells in vitro could be demonstrated to be lysed in a MHC class I-restricted manner. These findings provide evidence that virus-infected neurons can be destructed by T cell mediated cytotoxicity which results in organ atrophy and dementia.


Brain Cell Brain Atrophy Cell Mediate Cytotoxicity Lymphocytic Choriomeningitis Lymphocytic Choriomeningitis Virus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    Baenziger J, Hengartner H, Zinkernagel RM, Cole GA (1986) Induction or prevention of immunopathological disease by cloned cytotoxic T-cell line specific for lymphocytic choriomeningitis virus. Eur J Immunol 16: 387–393PubMedCrossRefGoogle Scholar
  2. 2.
    Byrne JA, Oldstone MBA (1984) Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: virus clearance in vivo. J Virol 51: 682–686PubMedGoogle Scholar
  3. 3.
    Carbone KM, Trapp BD, Griffin JW, Duchala CS, Narayan 0 (1989) Astrocytes and Schwann cells are virus host cells in the nervous system of rats with Borna disease. J Neuropathol Exp Neurol 48: 631–644Google Scholar
  4. 4.
    Carbone KM, Park SW, Rubin SA, Waltrip RW II, Vogelsang GB (1991) Borna disease: Association with a maturation defect in the cellular immune response. J Virol 65: 6154–6164PubMedGoogle Scholar
  5. 5.
    Cole GA, Nathanson N, Prendergast RA (1972) Requirement for Q-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature 238: 335–337PubMedCrossRefGoogle Scholar
  6. 6.
    Deschl U, Stitz L, Herzog S, Frese K, Rott R (1990) Determination of immune cells and expression of major histocompatibility complex class II antigen in encephalitic lesions of experimental Borna disease. Acta Neuropathol 81: 41–50PubMedCrossRefGoogle Scholar
  7. 7.
    Herzog S, Rott R (1980) Replication of Borna disease virus in cell cultures. Med Microbiol Immunol 168: 153–158PubMedCrossRefGoogle Scholar
  8. 8.
    Irigoin C, Rodriguez EM, Heinrichs M, Frese K, Herzog S, Oksche A, Rott R (1990) Immunocytochemical study of the subcommissural organ of rats with induced postnatal hydrocephalus. Exp Brain Res 82: 384–392PubMedCrossRefGoogle Scholar
  9. 9.
    Lipkin WI, Travis GH, Carbone KM, Wilson CM (1990) Isolation and characterization of Borna disease agent cDNA clones. Proc Natl Acad Sci USA 87: 4184–4188PubMedCrossRefGoogle Scholar
  10. 10.
    Moskophidis D, Cobbold SP, Waldmann H, Lehmann-Grube F (1987) Mechanism of recovery from acute virus infection: Treatment of lymphocytic choriomeningitis virus-infected mice with monoclonal antibodies reveals that Lyt-2+ T-lymphocytes mediate clearance and regulate the antiviral antibody response. J Virol 61: 1867–1874PubMedGoogle Scholar
  11. 11.
    Narayan O, Herzog S, Frese K, Scheefers H, Rott R (1983) Pathogenesis of Borna disease in rats: Immune-mediated viral ophtalmoencephalopathy causing blindness and behavioral abnormalities. J Infect Dis 148: 305–315Google Scholar
  12. 12.
    Narayan O, Herzog S, Frese K, Scheefers K, Rott R (1983) Behavioural disease in rats caused by immunopathological response to persistent Borna virus in the brain. Science 220: 1401–1403PubMedCrossRefGoogle Scholar
  13. 13.
    Planz O, Bilzer T, Sobbe M, Stitz L (1993) Lysis of MHC class I bearing cells in Borna disease virus-induced degenerative encephalopathy. J Exp Med 178: 163–174PubMedCrossRefGoogle Scholar
  14. 14.
    Richt JA, Stitz L, Wekerle K, Rott R (1989) Borna disease, a progressive meningoencephalitis as a model for CD4+ T-cell mediated immunopathology in the brain. J Exp Med 170: 1045–1050PubMedCrossRefGoogle Scholar
  15. 15.
    Rott R, Herzog S, Richt J, Stitz L (1989) Immune-mediated pathogenesis of Borna disease. Zentralbl Bakteriolog Mikrobiolog Hyg (A) 270: 295–301Google Scholar
  16. 16.
    Stitz L, Bilzer T, Richt J, Rott R (1993) Pathogenesis of Borna disease. In: Kaaden OR, Eichhorn W, Czerny CP (eds) Unconventional agents and unclassified viruses Arch Virol [Suppl] 7. Springer, Wien New York, pp 135–152Google Scholar
  17. 17.
    Stitz L, Planz O, Bilzer T, Frey K, Fontana A (1991) Transforming growth factor-beta modulates T-cell-mediated encephalitis caused by Borna disease virus. Pathogenetic importance of CD8+ cells and suppression of antibody formation. J Immunol 147: 3581–3586PubMedGoogle Scholar
  18. 18.
    Stitz L, Sobbe M, Bilzer T (1992) Preventive effects of early anti-CD4 or anti-CD8 treatment on Borna disease in rats. J Virol 66: 3316–3323PubMedGoogle Scholar
  19. 19.
    VanDeWoude S, Richt JA, Zink MC, Rott R, Narayan O, Clements JE (1990) A Borna virus cDNA encoding a protein recognized by antibodies in humans with behavioral disease. Science 250: 1278–1281PubMedCrossRefGoogle Scholar
  20. 20.
    Zinkernagel RM, Welsh RM (1976) H-2 compatibility requirement for virus specific T-cell-mediated effector functions in vivo. I. Specifity of T-cells conferring antiviral protection against lymphocytic choriomeningitis virus is associated with H2 K and H-2 D. J Immunol 117: 1495–1502PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • T. Bilzer
    • 1
    • 3
  • L. Stitz
    • 2
  1. 1.Department of NeuropathologyHeinrich-Heine-Universität DüsseldorfDüsseldorfFederal Republic of Germany
  2. 2.Institute of VirologyJustus-Liebig-Universität GiessenGiessenFederal Republic of Germany
  3. 3.Department of NeuropathologyHeinrich-Heine-Universität DüsseldorfDüsseldorfFederal Republic of Germany

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