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.