Home LiteratureArticle Details
PMID: 8878437 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The Journal of clinical investigation ·Vol. 98 ·No. 8 ·1996-10-15 ·Pages 1851-9

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

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.

MeSH Terms
Adoptive Transfer Animals Cyclophosphamide/pharmacology Diabetes Mellitus, Type 1/prevention & control Gene Transfer Techniques Genetic Therapy Interferon-gamma/genetics Interleukin-10/genetics,physiology Islets of Langerhans/pathology Mice Mice, Inbred NOD Polymerase Chain Reaction RNA, Messenger/analysis Th1 Cells/immunology
Chemicals
RNA, Messenger Interleukin-10 Interferon-gamma Cyclophosphamide
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Moritani M
Otsuka Department of Clinical and Molecular Nutrition, School of Medicine, The University of Tokushima, Japan.
Yoshimoto K
Ii S
Kondo M
Iwahana H
Yamaoka T
Sano T
Nakano N
Kikutani H
Itakura M
References (41)
41 references, click to expand
  1. Pancreatic islet-specific T-cell clones from nonobese diabetic mice.
    Proc Natl Acad Sci U S A. 1989 Oct;86(20):8000-4 PMID: 2510155
  2. Reciprocal allogeneic bone marrow transplantation between NOD mice and diabetes-nonsusceptible mice associated with transfer and prevention of autoimmune diabetes.
    Diabetes. 1989 Jul;38(7):894-901 PMID: 2661286
  3. Immunostimulation circumvents diabetes in NOD/Lt mice.
    J Autoimmun. 1989 Dec;2(6):759-76 PMID: 2533502
  4. Interleukin-2-dependent control of disease development in spontaneously diabetic BB rats.
    Immunology. 1990 Feb;69(2):209-14 PMID: 2307481
  5. Type-I diabetes: a chronic autoimmune disease of human, mouse, and rat.
    Annu Rev Immunol. 1990;8:647-79 PMID: 2188676
  6. Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line.
    Nucleic Acids Res. 1990 Jun 25;18(12):3587-96 PMID: 2194165
  7. Acceleration of diabetes in young NOD mice with a CD4+ islet-specific T cell clone.
    Science. 1990 Sep 21;249(4975):1433-6 PMID: 2205920
  8. Essential role for interferon-gamma and interleukin-6 in autoimmune insulin-dependent diabetes in NOD/Wehi mice.
    J Clin Invest. 1991 Feb;87(2):739-42 PMID: 1899431
  9. T cell receptor V gene usage of islet beta cell-reactive T cells is not restricted in non-obese diabetic mice.
    J Exp Med. 1991 May 1;173(5):1091-7 PMID: 1902501
  10. Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma.
    J Autoimmun. 1991 Apr;4(2):237-48 PMID: 1909135
  11. Somatic gene therapy for diabetes with an immunological safety system for complete removal of transplanted cells.
    Diabetes. 1992 Aug;41(8):956-61 PMID: 1628770
  12. Human TH1 and TH2 subsets: regulation of differentiation and role in protection and immunopathology.
    Int Arch Allergy Immunol. 1992;98(4):279-85 PMID: 1422257
  13. Prevention of autoimmune diabetes with lymphotoxin in NOD mice.
    Diabetes. 1993 Mar;42(3):398-404 PMID: 8432410
  14. Differential regulation of murine T lymphocyte subsets.
    Annu Rev Immunol. 1993;11:29-48 PMID: 8476563
  15. Interleukin 4 reverses T cell proliferative unresponsiveness and prevents the onset of diabetes in nonobese diabetic mice.
    J Exp Med. 1993 Jul 1;178(1):87-99 PMID: 8315397
  16. Induction of type I diabetes by interferon-alpha in transgenic mice.
    Science. 1993 Jun 25;260(5116):1942-6 PMID: 8100367
  17. Cytokine regulation of T-cell function: potential for therapeutic intervention.
    Immunol Today. 1993 Jun;14(6):270-4 PMID: 8104408
  18. The development of gene therapy for the treatment of cancer.
    Ann Surg. 1993 Oct;218(4):455-63; discussion 463-4 PMID: 8215637
  19. Pancreatic islet production of murine interleukin-10 does not inhibit immune-mediated tissue destruction.
    J Clin Invest. 1994 Mar;93(3):1332-8 PMID: 8132775
  20. Production of interleukin 10 by islet cells accelerates immune-mediated destruction of beta cells in nonobese diabetic mice.
    J Exp Med. 1994 Apr 1;179(4):1379-84 PMID: 8145050
  21. Recombinant human IL-10 prevents the onset of diabetes in the nonobese diabetic mouse.
    Clin Immunol Immunopathol. 1994 May;71(2):169-75 PMID: 8181185
  22. Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process.
    J Exp Med. 1994 Sep 1;180(3):995-1004 PMID: 8064245
  23. Properties and functions of interleukin-10.
    Adv Immunol. 1994;56:1-26 PMID: 8073945
  24. Transgenic expression of IL-10 in pancreatic islet A cells accelerates autoimmune insulitis and diabetes in non-obese diabetic mice.
    Int Immunol. 1994 Dec;6(12):1927-36 PMID: 7696210
  25. T helper cell subsets in insulin-dependent diabetes.
    Science. 1995 May 26;268(5214):1185-8 PMID: 7761837
  26. CD8 T cell clones from young nonobese diabetic (NOD) islets can transfer rapid onset of diabetes in NOD mice in the absence of CD4 cells.
    J Exp Med. 1996 Jan 1;183(1):67-76 PMID: 8551245
  27. Promotion of spontaneous diabetes in non-obese diabetes-prone mice by cyclophosphamide.
    Diabetologia. 1984 Dec;27(6):604-6 PMID: 6530055
  28. Cytokines cause functional and structural damage to isolated islets of Langerhans.
    Allergy. 1985 Aug;40(6):424-9 PMID: 3901813
  29. Transfer of autoimmune diabetes mellitus with splenocytes from nonobese diabetic (NOD) mice.
    Diabetes. 1986 Aug;35(8):855-60 PMID: 3525284
  30. Implantation of genetically engineered fibroblasts into mice: implications for gene therapy.
    Science. 1987 May 8;236(4802):714-8 PMID: 3472348
  31. Syngeneic transfer of autoimmune diabetes from diabetic NOD mice to healthy neonates. Requirement for both L3T4+ and Lyt-2+ T cells.
    J Exp Med. 1987 Oct 1;166(4):823-32 PMID: 3309126
  32. Destruction of rat islet cell monolayers by cytokines. Synergistic interactions of interferon-gamma, tumor necrosis factor, lymphotoxin, and interleukin 1.
    Diabetes. 1988 Jan;37(1):133-6 PMID: 3121415
  33. Both the Lyt-2+ and L3T4+ T cell subsets are required for the transfer of diabetes in nonobese diabetic mice.
    J Immunol. 1988 Jan 1;140(1):52-8 PMID: 3275717
  34. SR alpha promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat.
    Mol Cell Biol. 1988 Jan;8(1):466-72 PMID: 2827008
  35. Insulin-dependent diabetes mellitus induced in transgenic mice by ectopic expression of class II MHC and interferon-gamma.
    Cell. 1988 Mar 11;52(5):773-82 PMID: 2449974
  36. Anti-suppressor effect of cyclophosphamide on the development of spontaneous diabetes in NOD mice.
    Eur J Immunol. 1988 Mar;18(3):481-4 PMID: 2965652
  37. NOD marrow stem cells adoptively transfer diabetes to resistant (NOD x NON)F1 mice.
    Diabetes. 1988 Feb;37(2):252-5 PMID: 3134263
  38. Safe and efficient generation of recombinant retroviruses with amphotropic and ecotropic host ranges.
    Proc Natl Acad Sci U S A. 1988 Sep;85(17):6460-4 PMID: 3413107
  39. Descriptive and mechanistic considerations of interleukin 1 and insulin secretion.
    Diabetes. 1988 Oct;37(10):1311-5 PMID: 3046964
  40. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties.
    Annu Rev Immunol. 1989;7:145-73 PMID: 2523712
  41. Prevention of diabetes in nonobese diabetic mice by tumor necrosis factor (TNF): similarities between TNF-alpha and interleukin 1.
    Proc Natl Acad Sci U S A. 1990 Feb;87(3):968-72 PMID: 2405400
Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI118986
Published
1996-10-15
Pages
1851-9
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC507625
Subset
IM
External Links
PubMed source DOI: 10.1172/JCI118986 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2