ID 109646
Author
Moritani, Maki Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima
Yoshimoto, Katsuhiko Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Ii, Setsuko Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima
Kondo, Maki Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima
Iwahana, Hiroyuki Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima
Yamaoka, Takashi Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima
Sano, Toshiaki Department of Pathology, School of Medicine, The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Nakano, Naoko The Institute for Molecular and Cellular Biology, Osaka University
Kikutani, Hitoshi The Institute for Molecular and Cellular Biology, Osaka University
Itakura, Mitsuo Otsuka Department of Clinical and Molecular Nutrition, The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Keywords
insulin-dependent diabetes mellitus
insulitis
Th2
pancreatic islet B cells (islet B-cells)
somatic gene therapy
Content Type
Journal Article
Description
Four pancreatic islet-specific CD4+ helper T (Th) 1 (Th1) clones and two Th1 clones transduced with an SRα promoter-linked murine IL-10 (mIL-10) cDNA of 2.0–6.0×10[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 reversetranscription (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-γ 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-γ 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.
Journal Title
Journal of Clinical Investigation
ISSN
00219738
NCID
AA00695520
Volume
98
Issue
8
Start Page
1851
End Page
1859
Sort Key
1851
Published Date
1996-10-15
Remark
© The American Society for Clinical Investigation, Inc.
EDB ID
Published Source
Journal of Clinical Investigation (1996) Vol.98 No.8 p.1851–1859
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences
Medical Sciences
Institute of Advanced Medical Sciences