Lysis of major histocompatibility complex class I-bearing cells in Borna disease virus-induced degenerative encephalopathy.

Abstract

SummaryCD8 + as well as CD4 + T cells and macrophages are of crucial importance for the pathogenesis of Borna disease in rats. This virus-induced immunopathological disease of the brain is characterized by neurological symptoms in the acute phase and chronic debility associated with severe loss of brain tissue in the late stage. We demonstrate here the cytotoxic activity of T lymphocytes in the brain of intracerebrally infected rats. T cells isolated from the brain of infected rats lyse major histocompatibility complex (MHC) class I-bearing target cells in the absence of MHC class II. Borna disease virus (BDV)-infected syngeneic skin cells and astrocytes, the latter one of the relevant target cells in vivo, were significantly lysed whereas infected allogeneic target cells were not. Most relevant to the in vivo situation, primary brain cell cultures propagated from the hippocampus of BDV-infected rats containing considerable numbers of neurons were lysed in vitro. Blocking experiments using antibodies directed against MHC class I antigen provided further evidence for the presence and activity of classical cytotoxic T lymphocytes. Antibodies against MHC class II antigen did not influence lysis of skin target cells but had an effect on lysis of astrocytes at late time points. Lymphocytes isolated from spleen, peripheral blood, or lymph nodes did not show cytotoxic activity. These results verify, on the cellular level, earlier findings that strongly suggest the involvement of CD8 + T cells in brain cell lesions, resulting in brain atrophy long after infection of rats with BDV. This is further evidenced by the presence of CD8 + T cells in direct proximity to neuronal cell lesions. Interestingly, the cytolytic capacity, demonstrated in vitro and strongly correlated to organ destruction, does not result in elimination of the virus but the virus persists in the central nervous system.

Highly Pathogenic Influenza Virus Infection of the Thymus Interferes with T Lymphocyte Development

“…After 5 h, supernatant was collected and measured for the presence of released [ 51 Cr] using the microb counter (Wallac, PerkinElmer, Rodgau, Germany). The percentage of [ 51 Cr] release was calculated according to the formula previously described (27).…”

Amplification of a Full‐Length Borna Disease Virus (BDV) cDNA from Total RNA of Cells Persistently Infected with BDV

“…It replicates preferentially in cells derived from the neural crest (16). By co-cultivation of BDV-infected horse brain, not only neural cells but also other types of cells such as astrocytes (26) and skin cells (24) can be infected persistently. The virus can also be experimentally transmitted to other species, including birds and nonhuman primates, by intracranial and/or intranasal inoculation of homogenates of either brains of infected animals or persistently infected cultured cells.…”

High-Dose Borna Disease Virus Infection Induces a Nucleoprotein-Specific Cytotoxic T-Lymphocyte Response and Prevention of Immunopathology

“…In BD, T cells represent the major pathway of immunopathology; CD4 ϩ and, particularly, CD8 ϩ T cells are involved in severe encephalitis and the ensuing degenerative encephalopathy (2,10,23,24,29). On the other hand, immunoprotection is mediated by T cells (28), where CD8 ϩ cytotoxic T cells were again demonstrated as the relevant effector cells (20).…”

“…Lymphocytes from the brain were isolated by a method described previously (23). Briefly, animals were anesthetized and perfused with balanced salt solution.…”