title: Cytotoxicity of glioblastoma cells mediated ex vivo by varicella-zoster virus-specific T cells.
abstract: Clinical or laboratory evidence of varicella-zoster virus (VZV) infection has been consistently associated with lower glioma risk in case-control studies, suggesting a protective effect of VZV against glioma. We formulated the following explanatory hypotheses: reactivated VZV preferentially infects and kills gliomas compared to normal parenchyma; and VZV-specific cytotoxic T lymphocytes (CTL) cross-react with gliomas. We established an ex vivo model of VZV infection, which showed that glioma cell lines and primary astrocytes were equally permissive to VZV infection and had similar 15% average decrease in viability upon infection. In co-cultures, the relative growth of glioma cells and astrocytes was not affected by the VZV infection. However, VZV stimulated, but not mock stimulated, peripheral blood mononuclear cells from VZV-seropositive individuals recognized and killed HLA class I-matched glioma cells (mean±SE decrease in viability of 26 ± 12%, p = 0.04), but not matched astrocytes. VZV infection of the glioma cells did not affect the T cell-mediated killing. Taken together, these data suggest that ex vivo VZV infection has similar direct effects on glioma cells and astrocytes. The protective effect of prior VZV infection against the incidence of glioma may be mediated by CTL that recognizes epitopes shared by VZV and glioma cells.
authors.affiliation: Department of Pediatrics, University Colorado Denver School of Medicine, Denver, CO, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Canniff
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Donson
authors.forename: Nicholas K
authors.initials: NK
authors.lastname: Foreman
authors.forename: Adriana
authors.initials: A
authors.lastname: Weinberg
mesh_terms: D017209:Apoptosis; D001253:Astrocytes / Q000166:cytology / Q000821:virology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D005909:Glioblastoma / Q000276:immunology / Q000821:virology*; D006562:Herpes Zoster / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000821:virology; D014779:Virus Replication