dc.contributor.author | Dada, Shirine | |
dc.contributor.author | Wong, Masie | |
dc.contributor.author | Law, Kenneth | |
dc.contributor.author | Wu, Erxi | |
dc.contributor.author | Dunussi-Joannopoulos, Kyri | |
dc.contributor.author | Bluestone, Jeffrey | |
dc.contributor.author | Fiorina, Paolo | |
dc.contributor.author | Vergani, Andrea | |
dc.contributor.author | Jurewicz, Mollie | |
dc.contributor.author | Tian, Ze | |
dc.contributor.author | Abdi, Reza | |
dc.contributor.author | Guleria, Indira | |
dc.contributor.author | Rodig, Scott J. | |
dc.contributor.author | Sayegh, Mohamed Hassan | |
dc.date.accessioned | 2011-12-01T16:47:12Z | |
dc.date.issued | 2008 | |
dc.identifier.citation | Fiorina, Paolo, Andrea Vergani, Shirine Dada, Mollie Jurewicz, Masie Wong, Kenneth Law, Erxi Wu, et al. 2008. Targeting CD22 reprograms B-cells and reverses autoimmune diabetes. Diabetes 57(11): 3013-3024. | en_US |
dc.identifier.issn | 0012-1797 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:5358770 | |
dc.description.abstract | 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. | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | American Diabetes Association | en_US |
dc.relation.isversionof | doi:10.2337/db08-0420 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2570398/pdf/ | en_US |
dash.license | LAA | |
dc.title | Targeting CD22 Reprograms B-Cells and Reverses Autoimmune Diabetes | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | Diabetes | en_US |
dash.depositing.author | Fiorina, Paolo | |
dc.date.available | 2011-12-01T16:47:12Z | |
dash.affiliation.other | HMS^Pediatrics-Children's Hospital | en_US |
dash.affiliation.other | HMS^Pediatrics-Children's Hospital | en_US |
dash.affiliation.other | SPH^Genetics and Complex Diseases | en_US |
dash.affiliation.other | HMS^Medicine-Brigham and Women's Hospital | en_US |
dash.affiliation.other | HMS^Medicine-Brigham and Women's Hospital | en_US |
dc.identifier.doi | 10.2337/db08-0420 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Jurewicz, Mollie | |
dash.contributor.affiliated | Fiorina, Paolo | |
dash.contributor.affiliated | Vergani, Andrea | |
dash.contributor.affiliated | Tian, Ze | |
dash.contributor.affiliated | Abdi, Reza | |
dash.contributor.affiliated | Sayegh, Mohamed | |
dash.contributor.affiliated | Rodig, Scott | |
dash.contributor.affiliated | Guleria, Indira | |