TY - JOUR
T1 - Adenovirus vector delivery stimulates natural killer cell recognition
AU - Tomasec, Peter
AU - Wang, Eddie C Y
AU - Groh, Veronika
AU - Spies, Thomas
AU - McSharry, Brian P
AU - Aicheler, Rebecca J
AU - Stanton, Richard J
AU - Wilkinson, Gavin W G
PY - 2007/4
Y1 - 2007/4
N2 - 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, γ-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.
AB - 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, γ-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.
KW - Adenoviridae/immunology
KW - Cells, Cultured
KW - Cytotoxicity, Immunologic
KW - Fibroblasts/virology
KW - Genetic Vectors/immunology
KW - Humans
KW - Killer Cells, Natural/immunology
KW - NK Cell Lectin-Like Receptor Subfamily K
KW - Receptors, Immunologic/antagonists & inhibitors
KW - Receptors, Natural Killer Cell
UR - http://www.scopus.com/inward/record.url?scp=34047135584&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34047135584&partnerID=8YFLogxK
U2 - 10.1099/vir.0.82685-0
DO - 10.1099/vir.0.82685-0
M3 - Article
C2 - 17374753
AN - SCOPUS:34047135584
SN - 0022-1317
VL - 88
SP - 1103
EP - 1108
JO - Journal of General Virology
JF - Journal of General Virology
IS - 4
ER -