Borna disease virus-infected astrocytes function in vitro as antigen-presenting and target cells for virus-specific CD 4-bearing lymphocytes

Summary

Astrocytes isolated from the brain of newborn Lewis rats and an astrocytic cell line were susceptible to infection with the neurotropic Borna disease virus in vitro. Since astrocytes also have been found to be infected in vivo it seemed appropriate to test this cell type for interaction with a Borna disease virus-specific CD4⁺ T cell line. Borna disease virus-infected astrocytes were found to be capable of presenting virus-specific antigen to virus-specific T cells in vitro. However, the response was significantly enhanced if the purified 38/39 kDa Borna disease virus-specific protein was added exogenously to the cultures. Beside the function as antigen-presenting cells for various antigens including virus-specific protein and myelin basic protein, persistently infected astrocytes were also found to act as target cells for a CD4⁺ T cell line as shown in conventional⁵¹Cr release assays after induction of MHC class II expression by gamma interferon. Infection of astrocytes alone did not cause expression of this self antigen. It could be shown that the ability of CD4⁺ BDV-specific T cells to mediate lysis was in part dependent on the stage of activation. Lymphocytes “activated” before testing exerted high lysis after only 4h of coincubation with target cells, whereas “resting” T cells did not cause significant lysis until 12h of coincubation. The dependence of the interaction between effector and target cells on MHC class II antigen was demonstrated by the finding that antibodies to Ia antigens reduced lysis of target cells.