Adenovirus vector delivery stimulates natural killer cell recognition.
We report that delivery of first-generation replication-deficient adenovirus (RDAd) vectors into primary human fibroblasts is associated with the induction of natural killer (NK) cell-mediated cytolysis in vitro. RDAd vector delivery induced cytolysis by a range of NK cell populations including the NK cell clone NKL, primary polyclonal NK lines and a proportion of NK clones (36 %) in autologous HLA-matched assays. Adenovirus-induced cytolysis was inhibited by antibody blocking of the NK-activating receptor NKG2D, implicating this receptor in this function. NKG2D is ubiquitously expressed on NK cells and CD8(+) T cells. Significantly, gamma-irradiation of the vector eliminated the effect, suggesting that breakthrough expression from the vector induces at least some of the pro-inflammatory responses of unknown aetiology following the application of RDAd vectors during in vivo gene delivery.
Tomasec
Peter
P
Department of Medical Microbiology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Wang
Eddie C Y
ECY
Department of Medical Biochemistry and Immunology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Groh
Veronika
V
Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA98109, USA.
Spies
Thomas
T
Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA98109, USA.
McSharry
Brian P
BP
Department of Medical Microbiology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Aicheler
Rebecca J
RJ
Department of Medical Microbiology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Stanton
Richard J
RJ
Department of Medical Microbiology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
Wilkinson
Gavin W G
GWG
Department of Medical Microbiology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
D000256:Adenoviridae / Q000276:immunology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts / Q000821:virology; D005822:Genetic Vectors / Q000276:immunology*; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors; D055607:Receptors, Natural Killer Cell
C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell