Abstract
The inflammatory cell composition and the expression of major histocompatibility complex (MHC) antigens in the central nervous system (CNS) of 13 cats with a spontaneous, Borna disease-like meningoencephalomyelitis (staggering disease) was investigated by immunohistochemistry with a panel of monoclonal and polyclonal antibodies. T lymphocytes were the predominating inflammatory cells within the adventitial space. CD4+ T cells were more abundant than CD8+ T cells. Scattered IgG-, IgA- and IgM-containing cells were found in the adventitial space and surrounding neuropil, often adjacent to neurons. There was a markedly increased MHC class II expression in cells morphologically resembling microglia. In several cats, Borna disease virus specific antigen was detected, but only in a few cells, mainly of macrophage character. Our findings indicate a long-standing inflammatory reaction in the CNS of cats with staggering disease, possibly triggered and sustained by a persistent viral infection.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Ackley CD, Hoover EY, Cooper MD (1990) Identification of a CD4 homologue in the cat. Tissue Antigens 35: 92–98
Bilzer T, Stitz L (1994) Immune-mediated brain atrophy. CD8+ T cells contribute to tissue destruction during Borna Disease. J Immunol 153:818–823
Bode L, Riegel S, Lange W, Ludwig H (1992) Human infections with Borna disease virus: seroprevalence in patients with chronic disease and healthy individuals. J Med Virol 36: 309–315
Bode L, Dürrwald R, Ludwig H (1994) Borna virus infections in cattle associated with fatal neurological disease. Vet Rec 135: 283–284
Bode L, Steinbach F, Ludwig H (1994) A novel marker for Borna disease virus infection. Lancet 343:297–298
Briese T, Schneemann A, Lewis AJ, Park YS, Kim S, Ludwig H, Lipkin WI (1994) Genomic organization of Borna disease virus. Proc Natl Acad Sci USA 91:4362–4367
Cordell JL, Falini B, Erber WN, Ghosh AK, Abdulaziz Z, Mac-Donald S, Pulford KAF, Stein H, Mason DY (1984) Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem 32:219–229
Cubitt B, Oldstone C, Torre JC de la (1994) Sequence and genome organization of Borna disease virus. J Virol 68:1382–1396
Czech-Schmidt G (1993) Borna-Virus Infektionen im Tiermodell: serologische, virologische und molekularbiologische Untersuchungen. Inaugural-Dissertation, Freie Universität, Berlin, Germany
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 81:41–50
Dietzschold B, Kao M, Zheng YM, Chen XY, Maul G, Fu ZF, Rupprecht CE, Koprowski H (1992) Delineation of putative mechanisms involved in antibody-mediated clearance of rabies virus from the central nervous system. Proc Natl Acad Sci USA 89:7252–7256
Esiri MM, Gay D (1990) Immunological and neuropathological significance of the Virchow-Robin space. J Neurol Sci 100:3–8
Felgenhauer K (1982) Differentiation of the humoral immune response in inflammatory diseases of the central nervous system. J Neurol 228:223–237
Flir K (1973) Encephalomyelitis bei Grosskatzen. DTW Dtsch Tierärztl Wochenschr 80:401–404
Gallyas F (1970) Silver staining of micro- and oligodendroglia by means of physical development. Acta Neuropathol (Berl) 16: 35–38
Gosztonyi G (1992) Acute viral encephalitis: a monocyte/macrophage induced disease? Clin Neuropathol 11:261–262
Gosztonyi G, Ludwig H (1984) Borna disease of horses: an immunohistological and virological study of naturally infected animals. Acta Neuropathol (Berl) 64:213–221
Gosztonyi G, Ludwig H (1995) Borna disease: neuropathology and pathogenesis. Curr Top Microbiol Immunol 190:40–72
Griffin DE, Levine B, Tyor W, Irani DN (1992) The immune response in viral encephalitis. Semin Immunol 4:111–119
Hoff EJ, Vandevelde M (1981) Non-suppurative encephalomyelitis in cats suggestive of a viral origin. Vet Pathol 18: 170–180
Hsu SM, Raine L, Fanger H (1981) The use of avidin-biotinperoxidae complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem 29:577–580
Irani DN, Griffin DE (1991) Isolation of brain parenchymal lymphocytes for flow cytometric analysis. J Immunol Methods 139:223–231
Klotz FW, Cooper MD (1986) A feline thymocyte antigen defined by a monoclonal antibody (FT2) identifies a subpopulation of non-helper cells capable of specific cytotoxicity. J Immunol 136:2510–2514
Kronevi T, Nordström M, Moreno W, Nilsson PO (1973) Feline ataxia due to nonsuppurative meningoencephalomyelitis of unknown aetiology. Nord Veterinaemed 26:720–725
Ludwig H, Kraft W, Kao M, Gosztonyi G, Dahme E, Krey H (1985) Borna-Virus-Infektion (Borna-Krankheit) bei natürlich und experimentall infizierten Tieren: ihre Bedeutung für Forschung und Praxis. Tierärztl Prax 13:421–453
Ludwig H, Bode L, Gosztonyi G (1988) Borna disease: a persistent virus infection of the central nervous system. Prog Med Virol 35:107–151
Ludwig H, Furuya K, Bode L, Klein N, Dürrwald R, Lee DS (1993) Biology and neurobiology of Borna disease virus (BDV), defined by antibodies, neutralizability and their pathogenic potential. Arch Virol [Suppl] 7:111–133
Lundgren AL (1992) Feline non-suppurative meningoencephalomyelitis. A clinical and pathological study. J Comp Pathol 107:411–425
Lundgren AL, Ludwig H (1993) Clinically diseased cats with non-suppurative meningoencephalomyelitis have Borna disease virus-specific antibodies. Acta Vet Scand 34:101–103
Malkinson M, Weisman Y, Bode L, Ludwig H (1993) Borna disease in ostriches. Vet Rec 133:304
Moretta L, Pende D, Bottino C et al. (1987) Human CD3+, 4−, 8− WT31 T lymphocyte populations expressing the putative cell receptor γ gene product. A limiting dilution and clonal analysis. Eur J Immunol 17:1229–1234
Neefjes JJ, Hensen EJ, Kroon TIP de, Ploegh HL (1986) A biochemical characterization of feline MHC products: unusually high expression of class II antigens on peripheral blood lymphocytes. Immunogenetics 23:341–347
Petrov S (1993) Analyse der entzündlichen Reaktion bei der experimentellen Borna-Encephalitis der Ratte. Inaugural-Dissertation, Freie Universität, Berlin, Germany
Rideout BA, Moore PF, Pedersen NC (1990) Distribution of MHC class II antigens in feline tissues and peripheral blood. Tissue Antigens 36:221–227
Roggendorf W, Sasaki S, Ludwig H (1983) Light microscopic and immunohistologic investigations on the brain of Borna Disease virus infected rabbits. Neuropathol Appl Neurobiol 9: 287–296
Rott R, Herzog S, Fleischer B, Winokur H, Amsterdam JD, Dyson W, Koprowski H (1985) Detection of serum antibodies to Borna disease virus in patients with psychiatric disorders. Science 228:755–756
Spencer JO, MacDonald TT, Diss TC, Walker-Smith JA, Ciclitira PJ, Isaacson PG (1989) Changes in intraepithelial lymphocyte subpopulations in coeliac disease and enteropathy associated T cell lymphoma (malignant histiocytosis of the intestine). Gut 30:339–346
Sternberger LA (1979) Immunocytochemistry, 2nd edn. Wiley, New York
Stitz L, Bilzer T, Richt JA, Rott R (1993) Pathogenesis of Borna disease. Arch Virol [Suppl] 7:135–151
Tipold A, Pfister H, Zurbriggen A, Vandevelde M (1994) Intrathecal synthesis of major immunoglobulin classes in inflammatory diseases of the canine CNS. Vet Immunol Immunopathol 42:149–159
Tompkins MB, Gebhard DH, Bingham HR, Hamilton MJ, Davis WC, Tompkins WAF (1990) Characterization of monoclonal antibodies to feline T lymphocytes and their use in the analysis of lymphocyte tissue distribution in the cat. Vet Immunol Immunopathol 26:305–317
Truyen U, Stockhofe-Zurwieden N, Kaaden OR, Pohlenz J (1990) A case report: encephalitis in lions. Pathological and virological findings. DTW Dtsch Tierärztl Wochenschr 97:89–91
Vandevelde M, Braund KG (1979) Polioencephalomyelitis in cats. Vet Pathol 16:420–427
Weissenböck H, Nowotny N, Zoher J (1994) Feline meningoencephalomyelitis (“Staggering disease”) in Österreich. Wien Tierärztl Monatsschr 81:195–201
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lundgren, A.L., Lindberg, R., Ludwig, H. et al. Immunoreactivity of the central nervous system in cats with a Borna disease-like meningoencephalomyelitis (staggering disease). Acta Neuropathol 90, 184–193 (1995). https://doi.org/10.1007/BF00294319
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00294319