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Role of viral antigens in destructive cellular immune responses to adenovirus vector-transduced cells in mouse lungs.

Publication ,  Journal Article
Yang, Y; Su, Q; Wilson, JM
Published in: Journal of virology
October 1996

Adenoviruses missing E1 have been used as gene delivery vectors to the lungs for the treatment of cystic fibrosis. Transient expression of the recombinant gene and the development of inflammation have been two major limitations to the application of first-generation recombinant adenoviruses for gene therapy. Studies with mouse models of liver- and lung-directed gene therapy suggested that CD8+ cytotoxic T lymphocytes (CTLs) are effectors that contribute to extinction of transgene expression. The precise antigens responsible for activation of CTLs have not been identified. In this study, we examine the relative contributions of viral proteins versus the transgene product to the activation of CTLs which eliminate transgene-containing cells in mouse lungs. Instillation of a lacZ-expressing virus into the lungs of C57BL/6 mice elicited CTL responses to both viral proteins and the transgene product, beta-galactosidase, which collectively contribute to loss of trans-gene expression in mouse airways. Similar results were obtained in two experimental models in which the animals should be tolerant to the transgene, i.e., lacZ virus delivered to an animal transgenic for lacZ and a virus expressing the liver-specific enzyme ornithine transcarbamylase administered to the lungs of various strains of immune-competent mice. These data confirm the hypothesis that CTLs specific for viral antigens contribute to the problem of transgene instability in mouse lungs and indicate that CTLs specific for transgene product alone cannot account for the observed problem.

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Published In

Journal of virology

DOI

EISSN

1098-5514

ISSN

0022-538X

Publication Date

October 1996

Volume

70

Issue

10

Start / End Page

7209 / 7212

Related Subject Headings

  • Virology
  • Mice, Inbred C57BL
  • Mice
  • Lung
  • Lac Operon
  • Immunity, Cellular
  • Genetic Vectors
  • Genetic Therapy
  • Gene Transfer Techniques
  • CD8-Positive T-Lymphocytes
 

Citation

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Yang, Y., Su, Q., & Wilson, J. M. (1996). Role of viral antigens in destructive cellular immune responses to adenovirus vector-transduced cells in mouse lungs. Journal of Virology, 70(10), 7209–7212. https://doi.org/10.1128/jvi.70.10.7209-7212.1996
Yang, Y., Q. Su, and J. M. Wilson. “Role of viral antigens in destructive cellular immune responses to adenovirus vector-transduced cells in mouse lungs.Journal of Virology 70, no. 10 (October 1996): 7209–12. https://doi.org/10.1128/jvi.70.10.7209-7212.1996.
Yang, Y., et al. “Role of viral antigens in destructive cellular immune responses to adenovirus vector-transduced cells in mouse lungs.Journal of Virology, vol. 70, no. 10, Oct. 1996, pp. 7209–12. Epmc, doi:10.1128/jvi.70.10.7209-7212.1996.

Published In

Journal of virology

DOI

EISSN

1098-5514

ISSN

0022-538X

Publication Date

October 1996

Volume

70

Issue

10

Start / End Page

7209 / 7212

Related Subject Headings

  • Virology
  • Mice, Inbred C57BL
  • Mice
  • Lung
  • Lac Operon
  • Immunity, Cellular
  • Genetic Vectors
  • Genetic Therapy
  • Gene Transfer Techniques
  • CD8-Positive T-Lymphocytes