Cited by 18Immune Cell Function and InteractionVirus-based gene therapy researchImmunotherapy and Immune Responses

Adenovirus vector delivery stimulates natural killer cell recognition

Open access
Tomasec, Peter, Wang, Eddie C. Y., Groh, Veronika, Spies, Thomas, McSharry, Brian P., Aicheler, Rebecca J., Stanton, Richard J., Wilkinson, Gavin W. G.·2007·Journal of General Virology

Abstract

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.

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  1. Nakajima, H., Cella, M., Langen, H., Friedlein, A. & Colonna, M. (1999). Activating interactions in human NK cell recognition: the role of 2B4–CD48. Eur J Immunol 29, 1676–1683. 10359122

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Authors
Tomasec, P., Wang, E. C. Y., Groh, V., Spies, T., McSharry, B. P., Aicheler, R. J., Stanton, R. J., & Wilkinson, G. W. G.
Affiliations
  • Department of Medical Microbiology, Cardiff University, Heath Park, Cardiff CF14 4XY, UK
  • Cardiff University (GB)
  • Fred Hutch Cancer Center (US)
Venue
Journal of General Virology
Published
2007-04-01
Volume
88
Issue
4
Pages
1103-1108
ISSN
  • 0022-1317 (ISSN-L)
  • 1465-2099
OpenAlex
W1964769874
Cited by
18
References
46
Citations by year
2025: 3 · 2019: 1 · 2018: 1 · 2017: 1 · 2015: 2 · 2014: 1 · 2012: 1
FWCI
0.99
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Journal of General Virology (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • ORCA Online Research @Cardiff (Cardiff University) (acceptedVersion)
  • Charles Sturt University Research Output (CRO) (submittedVersion, other-oa)
Funders
Wellcome Trust
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
Keywords
natural killer cells, NK cell-mediated cytolysis, NKG2D, fibroblasts, gene therapy vectors, gamma irradiation, pro-inflammatory response, CD8+ T cells
MeSH terms
Adenoviridae, Cells, Cultured, Cytotoxicity, Immunologic, Fibroblasts, Genetic Vectors, Humans, Killer Cells, Natural, Receptors, Immunologic, Receptors, Natural Killer Cell, NK Cell Lectin-Like Receptor Subfamily K

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