CXC chemokine ligand 10 DNA vaccination plus complete Freund's adjuvant reverses hyperglycemia in non-obese diabetic mice

Yoichi Oikawa, Akira Shimada, Yoshifumi Yamada, Yoshiaki Okubo, Takeshi Katsuki, Toshikatsu Shigihara, Jun Ichi Miyazaki, Shosaku Narumi, Hiroshi Itoh

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

OBJECTIVE: Complete Freund's Adjuvant (CFA) is known to arrest autoimmune diabetes development in non-obese diabetic (NOD) mice. However, CFA alone cannot induce effective remission in diabetic NOD mice. Previously, we reported that anti-CXC chemokine ligand 10 (CXCL10) antibody can promote beta-cell proliferation in NOD mice. In the present study, we aimed to examine whether anti-CXCL10 plus CFA treatment can effectively reverse autoimmune diabetes development. METHODS: Systemic supply of anti-CXCL10 antibody by CXCL10 DNA vaccination in combination with CFA injection was performed in new-onset diabetic NOD mice. Remission rate of diabetes, histological characteristics of residual insulitis lesions, residual beta-cell mass, and regulatory T cell population in local pancreas were examined. RESULTS: A high frequency of diabetes reversal was observed after combination treatment with anti-CXCL10 plus CFA. In mice showing diabetes reversal, residual beta-cell mass was significantly increased, and some beta-cells were in a proliferative state. Although systemic cytokine profiles were unaffected, the frequency of "hybrid regulatory T cells", i.e. regulatory T cells expressing CXCR3, was significantly increased in local pancreatic lesions. This was possibly associated with the regulation of anti-islet autoimmunity. CONCLUSIONS: Anti-CXCL10 plus appropriate immune adjuvant therapy arrested, and reversed, type 1 diabetes development.

Original languageEnglish
Pages (from-to)198-213
Number of pages16
JournalReview of Diabetic Studies
Volume7
Issue number3
DOIs
Publication statusPublished - 2010 Sep

Fingerprint

CXC Chemokines
Inbred NOD Mouse
Freund's Adjuvant
Hyperglycemia
Vaccination
Ligands
DNA
Regulatory T-Lymphocytes
Type 1 Diabetes Mellitus
Antibodies
Autoimmunity
Pancreas
Therapeutics
Cell Proliferation
Cytokines
Injections
Population

Keywords

  • Beta-cell proliferation
  • Complete freund's adjuvant
  • CXC chemokine ligand 10
  • DNA accination
  • NOD mouse
  • Regulatory T cell
  • Type 1 diabetes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Internal Medicine

Cite this

CXC chemokine ligand 10 DNA vaccination plus complete Freund's adjuvant reverses hyperglycemia in non-obese diabetic mice. / Oikawa, Yoichi; Shimada, Akira; Yamada, Yoshifumi; Okubo, Yoshiaki; Katsuki, Takeshi; Shigihara, Toshikatsu; Miyazaki, Jun Ichi; Narumi, Shosaku; Itoh, Hiroshi.

In: Review of Diabetic Studies, Vol. 7, No. 3, 09.2010, p. 198-213.

Research output: Contribution to journalArticle

Oikawa, Y, Shimada, A, Yamada, Y, Okubo, Y, Katsuki, T, Shigihara, T, Miyazaki, JI, Narumi, S & Itoh, H 2010, 'CXC chemokine ligand 10 DNA vaccination plus complete Freund's adjuvant reverses hyperglycemia in non-obese diabetic mice', Review of Diabetic Studies, vol. 7, no. 3, pp. 198-213. https://doi.org/10.1900/RDS.2010.7.198
Oikawa, Yoichi ; Shimada, Akira ; Yamada, Yoshifumi ; Okubo, Yoshiaki ; Katsuki, Takeshi ; Shigihara, Toshikatsu ; Miyazaki, Jun Ichi ; Narumi, Shosaku ; Itoh, Hiroshi. / CXC chemokine ligand 10 DNA vaccination plus complete Freund's adjuvant reverses hyperglycemia in non-obese diabetic mice. In: Review of Diabetic Studies. 2010 ; Vol. 7, No. 3. pp. 198-213.
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