Advertisement

Research Article Free access | 10.1172/JCI2675

Local expression of immunoregulatory IL-12p40 gene prolonged syngeneic islet graft survival in diabetic NOD mice.

H Yasuda, M Nagata, K Arisawa, R Yoshida, K Fujihira, N Okamoto, H Moriyama, M Miki, I Saito, H Hamada, K Yokono, and M Kasuga

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Yasuda, H. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Nagata, M. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Arisawa, K. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Yoshida, R. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Fujihira, K. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Okamoto, N. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Moriyama, H. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Miki, M. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Saito, I. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Hamada, H. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Yokono, K. in: PubMed | Google Scholar

Second Department of Internal Medicine, Kobe University School of Medicine, Kobe 650-0017, Japan.

Find articles by Kasuga, M. in: PubMed | Google Scholar

Published November 15, 1998 - More info

Published in Volume 102, Issue 10 on November 15, 1998
J Clin Invest. 1998;102(10):1807–1814. https://doi.org/10.1172/JCI2675.
© 1998 The American Society for Clinical Investigation
Published November 15, 1998 - Version history
View PDF
Abstract

Local production of immunosuppressive cytokines will be one of the most suitable therapeutic strategies against organ-specific autoimmune diabetes. To establish such a new therapy, we constructed recombinant adenoviral vectors with inserted mIL-12p40 (Ad.IL-12p40) and mIL-10 (Ad.IL-10). Sufficient amounts of IL-12p40 and IL-10 were secreted by relevant adenovirus-transfected nonobese diabetic (NOD) islets. Shortly after transfection, 400 NOD islets transfected with Ad.IL-12p40 or Ad.IL-10 were transplanted under the renal capsule of a newly diabetic NOD mouse. NOD mice with IL-12p40-producing islet grafts kept normoglycemia in all of 14 grafted mice for over 4 wk after transplantation. In contrast, NOD mice with IL-10-producing islet grafts became diabetic in all of six grafted mice within 2 wk af-ter transplantation. Reverse transcription-PCR analysis revealed that local production of IL-12p40 led to the decrease of interferon-gamma and the augmentation of transforming growth factor-beta at the graft site. These results suggest that IL-12 plays an important role in the destruction of islet cells at the inflamed site of autoimmunity. Such a local blockade of IL-12 would be a useful gene therapy for human autoimmune diabetes.

Version history
  • Version 1 (November 15, 1998): No description
Advertisement
Advertisement