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Tissue-specific consequences of the anti-adenoviral immune response: implications for cardiac transplants

Nature Medicine volume 5, pages 1143–1149 (1999)Cite this article

Abstract

The immune response to adenoviral vectors can induce inflammation and loss of transgene expression in transfected tissues. This would limit the use of adenovirus-mediated gene transfer in disease states in which long-term gene expression is required. While studying the effect of the anti-adenoviral immune response in transplantation, we found that transgene expression persisted in cardiac isografts transfected with an adenovirus encoding β-galactosidase. Transfected grafts remained free of inflammation, despite the presence of an immune response to the vector. Thus, adenovirus-mediated gene transfer may have therapeutic value in cardiac transplantation and heart diseases. Furthermore, immunological limitations of adenoviral vectors for gene therapy are not universal for all tissue types.

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Figure 1: Inflammation and transgene expression after transplant or intravenous delivery of Ad.
Figure 2: Transient splenic transgene expression in recipients of Ad.
Figure 3: Cellular immunity after cardiac transplant or intravenous delivery of Ad.
Figure 4: Antibody responses against adenovirus after cardiac transplant or intravenous delivery of Ad.
Figure 5: Tissue distribution influences inflammation and transgene expression after transplant or intravenous delivery of Ad.
Figure 6: Transgene expression in Ad.

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Acknowledgements

We thank G. Nabel and M. Imperiale for their comments regarding this manuscript. This work was supported by NIH grant R01 AI HL 31946.

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Authors and Affiliations

  1. Department of Surgery University of Michigan School of Medicine, Section of General Surgery, Ann Arbor, 48109-0654, Michigan, USA

    Sherri Y. Chan, Kewang Li, Joseph R. Piccotti, Marisa C. Louie & D. Keith Bishop

  2. Department of Medicine, University of Pennsylvania, Philadelphia, 19104-6069, Pennsylvania, USA

    Thomas A. Judge & Laurence A. Turka

  3. Department of Pathology, University of Utah, Salt Lake City, 84132, Utah, USA

    Ernst J. Eichwald

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Correspondence to D. Keith Bishop.

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Chan, S., Li, K., Piccotti, J. et al. Tissue-specific consequences of the anti-adenoviral immune response: implications for cardiac transplants. Nat Med 5, 1143–1149 (1999). https://doi.org/10.1038/13467

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