Induction of anti-whole GAD65 reactivity in vivo results in disease suppression in type 1 diabetes

Yasuhiko Kanazawa, Akira Shimada, Yoichi Oikawa, Yoshiaki Okubo, Ai Tada, Takatoshi Imai, Junichi Miyazaki, Hiroshi Itoh

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Most type 1 diabetes mellitus is caused by autoimmune pancreatic beta-cell destruction. Several antigens such as insulin, glutamic acid decarboxylase (GAD) and islet-specific glucose-6-phosphatase catalytic subunit related protein (IGRP) are considered to take part in the autoimmune destructive process. Because the role of GAD in the disease process of type 1 diabetes is still controversial, we investigated the disease phenotype upon in vivo induction of whole GAD65 reactivity using a GAD65 homo knockout NOD splenocytes to NOD-scid transfer system. Splenocytes from 8 to 10-week-old female GAD65 homo knockout (=KOT splenocytes) or age-matched wild type (=WTT splenocytes) NOD mice were transferred into female NOD-scid recipients. As compared to recipients of WTT splenocytes, the onset of diabetes in recipients of KOT splenocytes was significantly delayed (p < 0.001). Moreover, TGF-β expression was enhanced in the pancreas from recipients of KOT splenocytes. Splenocytes from recipients of KOT splenocytes produced IL-10 (/IFN-γ) upon GAD65 stimulation, whereas those from recipients of WTT splenocytes did not. Based upon these results, we propose that anti-whole GAD65-reactive T cells have the ability to regulate the development of type 1 diabetes.

Original languageEnglish
Pages (from-to)104-109
Number of pages6
JournalJournal of Autoimmunity
Volume32
Issue number2
DOIs
Publication statusPublished - 2009 Mar

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Type 1 Diabetes Mellitus
Glutamate Decarboxylase
Glucose-6-Phosphatase
Inbred NOD Mouse
Insulin-Secreting Cells
Interleukin-10
Pancreas
Catalytic Domain
Insulin
T-Lymphocytes
Phenotype
Antigens
Proteins

Keywords

  • GAD65
  • Regulatory T cell
  • Type 1 diabetes

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Induction of anti-whole GAD65 reactivity in vivo results in disease suppression in type 1 diabetes. / Kanazawa, Yasuhiko; Shimada, Akira; Oikawa, Yoichi; Okubo, Yoshiaki; Tada, Ai; Imai, Takatoshi; Miyazaki, Junichi; Itoh, Hiroshi.

In: Journal of Autoimmunity, Vol. 32, No. 2, 03.2009, p. 104-109.

Research output: Contribution to journalArticle

Kanazawa, Y, Shimada, A, Oikawa, Y, Okubo, Y, Tada, A, Imai, T, Miyazaki, J & Itoh, H 2009, 'Induction of anti-whole GAD65 reactivity in vivo results in disease suppression in type 1 diabetes', Journal of Autoimmunity, vol. 32, no. 2, pp. 104-109. https://doi.org/10.1016/j.jaut.2009.01.001
Kanazawa, Yasuhiko ; Shimada, Akira ; Oikawa, Yoichi ; Okubo, Yoshiaki ; Tada, Ai ; Imai, Takatoshi ; Miyazaki, Junichi ; Itoh, Hiroshi. / Induction of anti-whole GAD65 reactivity in vivo results in disease suppression in type 1 diabetes. In: Journal of Autoimmunity. 2009 ; Vol. 32, No. 2. pp. 104-109.
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