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


     

Published online August 8, 2008
Diabetes 57:3013-3024, 2008
DOI: 10.2337/db08-0420
© 2008 by the American Diabetes Association
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Online-Only Appendix
Right arrow All Versions of this Article:
db08-0420v1
57/11/3013    most recent
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
Google Scholar
Right arrow Articles by Fiorina, P.
Right arrow Articles by Sayegh, M. H.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fiorina, P.
Right arrow Articles by Sayegh, M. H.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes

Paolo Fiorina1,2, Andrea Vergani1,2, Shirine Dada1, Mollie Jurewicz1, Masie Wong1, Kenneth Law3, Erxi Wu4, Ze Tian4, Reza Abdi1, Indira Guleria1, Scott Rodig3, Kyri Dunussi-Joannopoulos5, Jeffrey Bluestone6, and Mohamed H. Sayegh1

1 Transplantation Research Center, Children's Hospital and Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
2 Department of Medicine, San Raffaele Scientific Institute, Milan, Italy
3 Department of Pathology, Division of Hematopathology, Brigham & Women's Hospital, Harvard Medical School, Boston, Massachusetts
4 Children's Hospital Informatics Program at the Harvard-MIT Division of Health Sciences and Technology, Boston, Massachusetts
5 Inflammation, Wyeth Research, Cambridge, Massachusetts
6 University of California San Francisco Diabetes Center, San Francisco, California

Corresponding author: Mohamed H. Sayegh, msayegh{at}rics.bwh.harvard.edu

OBJECTIVES—To investigate a B-cell–depleting strategy to reverse diabetes in naïve NOD mice.

RESEARCH DESIGN AND METHODS—We targeted the CD22 receptor on B-cells of naïve NOD mice to deplete and reprogram B-cells to effectively reverse autoimmune diabetes.

RESULTS—Anti-CD22/cal monoclonal antibody (mAb) therapy resulted in early and prolonged B-cell depletion and delayed disease in pre-diabetic mice. Importantly, when new-onset hyperglycemic mice were treated with the anti-CD22/cal mAb, 100% of B-cell–depleted mice became normoglycemic by 2 days, and 70% of them maintained a state of long-term normoglycemia. Early therapy after onset of hyperglycemia and complete B-cell depletion are essential for optimal efficacy. Treated mice showed an increase in percentage of regulatory T-cells in islets and pancreatic lymph nodes and a diminished immune response to islet peptides in vitro. Transcriptome analysis of reemerging B-cells showed significant changes of a set of proinflammatory genes. Functionally, reemerging B-cells failed to present autoantigen and prevented diabetes when cotransferred with autoreactive CD4+ T-cells into NOD.SCID hosts.

CONCLUSIONS—Targeting CD22 depletes and reprograms B-cells and reverses autoimmune diabetes, thereby providing a blueprint for development of novel therapies to cure autoimmune 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 © 2008 by the American Diabetes Association.