CXC Chemokine Ligand 10 DNA Vaccination Plus Complete Freund’s Adjuvant Reverses Hyperglycemia in Non-Obese Diabetic Mice

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The Review of Diabetic Studies,2010,7,3,209-224.
Published:November 2010
Type:Original Article
Author(s) affiliations:

Yoichi Oikawa1,2, Akira Shimada1,2, Yoshifumi Yamada1, Yoshiaki Okubo1, Takeshi Katsuki1,2, Toshikatsu Shigihara1, Jun-ichi Miyazaki3, Shosaku Narumi4, and Hiroshi Itoh1

1Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.

2Department of Internal Medicine, Saiseikai Central Hospital, Tokyo, Japan.

3Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, Osaka, Japan.

4Stelic Institute and Corporation, Tokyo, Japan.


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 betacell 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. Conclusion: Anti-CXCL10 plus appropriate immune adjuvant therapy arrested, and reversed, type 1 diabetes development.