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 journalArticlepeer-review

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 1

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

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