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 - 2007/4/1
Y1 - 2007/4/1
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.
UR - http://www.scopus.com/inward/record.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 -