Prevention of adoptively transferred diabetes in nonobese diabetic mice with IL-10-transduced islet-specific Th1 lymphocytes. A gene therapy model for autoimmune diabetes. (original) (raw)

Research Article Free access | 10.1172/JCI118986

K Yoshimoto, S Ii, M Kondo, H Iwahana, T Yamaoka, T Sano, N Nakano, H Kikutani, and M Itakura

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

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

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

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

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

Find articles by Ii, S. in:JCI |PubMed |Google Scholar

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

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

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

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

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

Find articles by Yamaoka, T. in:JCI |PubMed |Google Scholar

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

Find articles by Sano, T. in:JCI |PubMed |Google Scholar

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

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

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

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

Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.

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

Published October 15, 1996 -More info

Published October 15, 1996 -Version history

View PDF

Abstract

Four pancreatic islet-specific CD4+ helper T (Th) 1 (Th1) clones and two Th1 clones transduced with an SRalpha promoter-linked murine IL-10 (mIL-10) cDNA of 2.0-6.0 x 10(6) cells were adoptively transferred to nonobese diabetic (NOD) mice at age 8 d. Cyclophosphamide (CY) was administered at age 37 d (plus CY), and the incidence of diabetes and the histological grade of insulitis were examined at age 47 d. After the adoptive transfer of IL-10-transduced Th1 cells, polymerase chain reaction (PCR) and reverse-transcription (RT)-PCR detected the neo gene and the retrovirus vector-mediated IL-10 mRNA in situ in recipient islets, respectively. RT-PCR detected the decrease of IFN-gamma mRNA relative to IL-10 mRNA in IL-10-transduced Th1 clones in vitro and also in recipient islets. All four wild type Th1 clones plus CY induced the insulitis grade of 2.75 and diabetes in 66% of recipient NOD mice. IL-10-transduced two Th1 clones plus CY induced periinsulitis with the grade of 1.43 and diabetes in 8.0%. The 1:1 mixture of wild type Th1 cells and IL-10-transduced Th1 cells plus CY induced periinsulitis with the grade of 1.85 and diabetes in 20%. The suppression of diabetes through decreasing IFN-gamma mRNA by the tissue-specific delivery of IL-10 to pancreatic islets with IL-10-transduced Th1 cells affords us the starting basis to develop the gene therapy for autoimmune diabetes.

Version history