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  • Acquired Diseases
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Immunotherapy of spontaneous type 1 diabetes in nonobese diabetic mice by systemic interleukin-4 treatment employing adenovirus vector-mediated gene transfer

Gene Therapy volume 7, pages 1840–1846 (2000)Cite this article

Abstract

We have previously shown that systemic injection of multiple low doses of recombinant murine interleukin-4 (mIL-4) can prevent type 1 diabetes (T1D) in nonobese diabetic (NOD) mice by activating regulatory T helper (Th) 2 cells in vivo. Here, we have developed a gene transfer approach to the prevention of T1D by testing the therapeutic potential of an adenovirus gene transfer vector engineered to express mIL-4. We found that only two systemic injections of a recombinant adenovirus type 5 vector-expressing mIL-4 (Ad5mIL-4) reduces destructive insulitis and protects NOD mice from the onset of diabetes by eliciting intrapancreatic Th2 cell responses. Host immune responses against the adenovirus vector were detectable; however, the levels of antibody production were insufficient to preclude Ad5mIL-4 treatment as a possible therapeutic agent against T1D. Thus, adenovirus-mediated delivery of IL-4 provides protection of NOD mice from T1D and represents a clinically viable therapeutic approach.

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Acknowledgements

We thank Dr Subrata Chakrabarti and Kollol Mukerjee for their assistance with the pancreas histology, Ms Carol Richardson and her staff for maintaining our mouse colony, Ms Anne Leaist for her cheerful assistance with the preparation of this manuscript, and all members of our laboratory for their advice and encouragement. Supported by grants from the Juvenile Diabetes Foundation International (JDFI), Medical Research Council (MRC) of Canada (MT-5729), MRC/JDFI Diabetes Centre of Excellence and Canadian Diabetes Association (CDA) (TLD), a postdoctoral fellowship from the CDA and Fundayacucho (Venezuela) (GAA), and a Doctoral Research Award from the MRC of Canada (MJC).

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Authors and Affiliations

  1. Autoimmunity/Diabetes Group, The John P Robarts Research Institute, London, Ontario, Canada

    M J Cameron, G A Arreaza & T L Delovitch

  2. Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada

    M J Cameron, G A Arreaza & T L Delovitch

  3. Department of Pathology, McMaster University, Hamilton, Ontario, Canada

    L Waldhauser & J Gauldie

  4. Department of Medicine, University of Western Ontario, London, Ontario, Canada

    T L Delovitch

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  1. M J Cameron
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  2. G A Arreaza
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  4. J Gauldie
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  5. T L Delovitch
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Cameron, M., Arreaza, G., Waldhauser, L. et al. Immunotherapy of spontaneous type 1 diabetes in nonobese diabetic mice by systemic interleukin-4 treatment employing adenovirus vector-mediated gene transfer. Gene Ther 7, 1840–1846 (2000). https://doi.org/10.1038/sj.gt.3301309

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