title: Influenza a virus induces an immediate cytotoxic activity in all major subsets of peripheral blood mononuclear cells.
abstract: BACKGROUND
  A replication defective influenza A vaccine virus (delNS1 virus) was developed. Its attenuation is due to potent stimulation of the innate immune system by the virus. Since the innate immune system can also target cancer cells, we reasoned that delNS1 virus induced immune-stimulation should also lead to the induction of innate cytotoxic effects towards cancer cells.
  
  
  RESULTS
  Peripheral blood mononuclear cells (PBMCs), isolated CD56+, CD3+, CD14+ and CD19+ subsets and different combinations of the above subsets were stimulated by delNS1, wild type (wt) virus or heat inactivated virus and co-cultured with tumor cell lines in the presence or absence of antibodies against the interferon system. Stimulation of PBMCs by the delNS1 virus effectively induced cytotoxicity against different cancer cell lines. Surprisingly, virus induced cytotoxicity was exerted by all major subtypes of PBMCs including CD56+, CD3+, CD14+ and CD19+ cells. Virus induced cytotoxicity in CD3+, CD14+ and CD19+ cells was dependent on virus replication, whereas virus induced cytotoxicity in CD56+ cells was only dependent on the binding of the virus. Virus induced cytotoxicity of isolated cell cultures of CD14+, CD19+ or CD56+ cells could be partially blocked by antibodies against type I and type II (IFN) interferon. In contrast, virus induced cytotoxicity in the complete PBMC preparation could not be inhibited by blocking type I or type II IFN, indicating a redundant system of activation in whole blood.
  
  
  CONCLUSIONS
  Our data suggest that apart from their well known specialized functions all main subsets of peripheral blood cells also initially exert a cytotoxic effect upon virus stimulation. This closely links the innate immune system to the adaptive immune response and renders delNS1 virus a potential therapeutic tool for viro-immunotherapy of cancer.
authors.affiliation: Division of General Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Sanda
authors.initials: S
authors.lastname: Sturlan
authors.forename: Monika
authors.initials: M
authors.lastname: Sachet
authors.forename: Suzann
authors.initials: S
authors.lastname: Baumann
authors.forename: Irina
authors.initials: I
authors.lastname: Kuznetsova
authors.forename: Andreas
authors.initials: A
authors.lastname: Spittler
authors.forename: Michael
authors.initials: M
authors.lastname: Bergmann
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D015415:Biomarkers / Q000378:metabolism; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D016207:Cytokines / Q000276:immunology; D003603:Cytotoxins / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology; D013154:Spleen / Q000166:cytology; D014779:Virus Replication
chemical_list: D015703:Antigens, CD; D015415:Biomarkers; D016207:Cytokines; D003603:Cytotoxins; D009838:Oligodeoxyribonucleotides