Transforming growth factor-beta modulates T cell-mediated encephalitis caused by Borna disease virus. Pathogenic importance of CD8+ cells and suppression of antibody formation.
Borna disease is a virus-induced, immune-mediated encephalomyelitis based on a delayed-type hypersensitivity reaction. The severity of clinical symptoms after intracerebral infection of rats with Borna disease virus was reduced after treatment with transforming growth factor (TGF-beta 2). Intraperitoneal injection of the recombinant molecule, rTGF-beta 2, started on the day of infection at a dose of either 1 micrograms given every day or every other day for 8 consecutive days or 2 micrograms every third day, was found to result in the absence of typical Borna disease symptoms at 14 days after infection in most of the TGF-beta-treated rats, a time point at which all infected control animals not treated with rTGF-beta 2 showed distinct signs of Borna disease. The inhibition of the disease was paralleled by a significant reduction of the inflammatory reaction in the brain. However, the efficacy of treatment with rTGF-beta 2 was transient, because after day 21 only a slight or no reduction of the inflammatory reaction and, consequently, symptoms of Borna disease could be observed. Immunohistologic investigations revealed reduced CD4+ T cell numbers and no changes in macrophage counts in encephalitic lesions of rTG-beta treated rats. However, CD8+ cells were markedly decreased in the encephalitic lesions. Furthermore, the expression of MHC class II Ag was significantly reduced in the brain of rTGF-beta 2 treated Borna disease virus-infected rats, whereas MHC class I Ag expression was not. Most treated animals showed a reduction of Borna disease virus-specific serum antibodies, the result of an inhibition of the IgG response. The results presented here suggest a distinct influence of rTGF-beta 2 on T cell-mediated immune functions during the early phase of Borna disease virus-induced encephalomyelitis.
Stitz
L
L
Institut für Virologie, Justus-Liebig-Universität Giessen, FRG.
Planz
O
O
Bilzer
T
T
Frei
K
K
Fontana
A
A
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D001890:Borna Disease / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D001891:Borna disease virus / Q000276:immunology; D001921:Brain / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016827:CD8 Antigens / Q000032:analysis; D004660:Encephalitis / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D006624:Hippocampus / Q000473:pathology; D006968:Hypersensitivity, Delayed / Q000276:immunology / Q000628:therapy; D007111:Immunity, Cellular / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*
D000956:Antigens, Viral; D016827:CD8 Antigens; D016212:Transforming Growth Factor beta