title: CXC chemokine ligand 10 DNA vaccination plus Complete Freund's Adjuvant reverses hyperglycemia in non-obese diabetic mice.
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.
authors.affiliation: Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. oikawa@saichu.jp
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oikawa
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Okubo
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katsuki
authors.forename: Toshikatsu
authors.initials: T
authors.lastname: Shigihara
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Miyazaki
authors.forename: Shosaku
authors.initials: S
authors.lastname: Narumi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Itoh
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use; D054357:Chemokine CXCL10 / Q000235:genetics / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D004195:Disease Models, Animal; D005260:Female; D005620:Freund's Adjuvant / Q000627:therapeutic use*; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control; D051379:Mice; D016688:Mice, Inbred NOD; D051381:Rats; D014611:Vaccination; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D054357:Chemokine CXCL10; D019444:Vaccines, DNA; D005620:Freund's Adjuvant