Open AccessAdenovirus vector delivery stimulates natural killer cell recognition
Author(s) -
Peter Tomašec,
Eddie C. Y. Wang,
Veronika Groh,
Thomas A. Spies,
Brian P. McSharry,
Rebecca Aicheler,
Richard J. Stanton,
Gavin W. G. Wilkinson
Publication year - 2007
Publication title -
journal of general virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.55
H-Index - 167
eISSN - 1465-2099
pISSN - 0022-1317
DOI - 10.1099/vir.0.82685-0
Subject(s) - biology , nkg2d , cytolysis , virology , cd8 , natural killer cell , clone (java method) , viral vector , gene delivery , interleukin 21 , cytotoxic t cell , polyclonal antibodies , janus kinase 3 , genetic enhancement , microbiology and biotechnology , in vitro , antibody , immunology , immune system , gene , recombinant dna , genetics
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.
Accelerating Research
Robert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom
Address
John Eccles HouseRobert Robinson Avenue,
Oxford Science Park, Oxford
OX4 4GP, United Kingdom