LYSIS OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I-BEARING CELLS IN BORNA-DISEASE VIRUS-INDUCED DEGENERATIVE ENCEPHALOPATHY

CD8+ as well as CD4+ T cells and macrophages are of crucial importance for the pathogenesis of Borna disease in rats. This virus-induced imm unopathological disease of the brain is characterized by neurological symptoms in the acute phase and chronic debility associated with sever e loss of brain tissue in the late stage. We demonstrate here the cyto toxic activity of T lymphocytes in the brain of intracerebrally infect ed rats. T cells isolated from the brain of infected rats lyse major h istocompatibility complex (MHC) class I-bearing target cells in the ab sence of MHC class II. Borna disease virus (BDV)-infected syngeneic sk in cells and astrocytes, the latter one of the relevant target cells i n vivo, were significantly lysed whereas infected allogeneic target ce lls were not. Most relevant to the in vivo situation, primary brain ce ll cultures propagated from the hippocampus of BDV-infected rats conta ining considerable numbers of neurons were lysed in vitro. Blocking ex periments using antibodies directed against MHC class I antigen provid ed further evidence for the presence and activity of classical cytotox ic T lymphocytes. Antibodies against MHC class II antigen did not infl uence lysis of skin target cells but had an effect on lysis of astrocy tes at late time points. Lymphocytes isolated from spleen, peripheral blood, or lymph nodes did not show cytotoxic activity. These results v erify, on the cellular level, earlier findings that strongly suggest t he involvement of CD8+ T cells in brain cell lesions, resulting in bra in atrophy long after infection of rats with BDV. This is further evid enced by the presence of CD8+ T cells in direct proximity to neuronal cell lesions. Interestingly, the cytolytic capacity, demonstrated in v itro and strongly correlated to organ destruction, does not result in elimination of the virus but the virus persists in the central nervous system.