Brain cell lesions in Borna disease are mediated by T cells

Abstract

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.