Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Diabetes 56:809-817, 2007
DOI: 10.2337/db06-0619
© 2007 by the American Diabetes Association
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online-Only Appendix
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Meagher, C.
Right arrow Articles by Delovitch, T. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Meagher, C.
Right arrow Articles by Delovitch, T. L.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

CCL4 Protects From Type 1 Diabetes by Altering Islet ß-Cell–Targeted Inflammatory Responses

Craig Meagher1,2, Guillermo Arreaza2, Andrew Peters3, Craig A. Strathdee4, Philippe A. Gilbert3, Qing-Sheng Mi3, Pere Santamaria5, Gregory A. Dekaban1,3, and Terry L. Delovitch1,2

1 Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada
2 Laboratory of Autoimmune Diabetes, Robarts Research Institute, London, Ontario, Canada
3 BioTherapeutics Research Group, Robarts Research Institute, London, Ontario, Canada
4 Amgen, Seattle, Washington
5 Julia McFarlane Diabetes Research Centre, University of Calgary, Calgary, Alberta, Canada

Address correspondence and reprint requests to Dr. Terry L. Delovitch, Laboratory of Autoimmune Diabetes, Robarts Research Institute, 100 Perth Dr., London, Ontario, N6A 5K8, Canada. E-mail: del{at}robarts.ca

Abbreviations: ELISA, enzyme-linked immunosorbent assay; FITC, fluorescein isothiocyanate; IGLN, inguinal lymph node; IL, interleukin; IFN, interferon; PLN, pancreatic draining lymph node; Treg, regulatory T

We previously reported that interleukin (IL)-4 treatment of nonobese diabetic (NOD) mice elevates intrapancreatic CCL4 expression and protects from type 1 diabetes. Here, we show that antibody neutralization of CCL4 abrogates the ability of T-cells from IL-4–treated NOD mice to transfer protection against type 1 diabetes. Intradermal delivery of CCL4 via a plasmid vector stabilized by incorporation of the Epstein-Barr virus EBNA1/oriP episomal maintenance replicon (pHERO8100-CCL4) to NOD mice beginning at later stages of disease progression protects against type 1 diabetes. This protection was associated with a Th2-like response in the spleen and pancreas; decreased recruitment of activated CD8+ T-cells to islets, accompanied by diminished CCR5 expression on CD8+ T-cells; and regulatory T-cell activity in the draining pancreatic lymph nodes. Thus, inflammatory responses that target islet ß-cells are suppressed by CCL4, which implicates the use of CCL4 therapeutically to prevent type 1 diabetes.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2007 by the American Diabetes Association.