HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: db06-1632v1 56/8/2103    most recent Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Ishikawa, H. Articles by Weiner, H. L. Search for Related Content PubMed PubMed Citation Articles by Ishikawa, H. Articles by Weiner, H. L. Social Bookmarking                What's this?

Inhibition of Autoimmune Diabetes by Oral Administration of Anti-CD3 Monoclonal Antibody

From the Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts

Address correspondence and reprint requests to Howard L. Weiner, Harvard Institutes of Medicine, Brigham and Women's Hospital, Neurology, Cnd/HIM, Room 730, 77 Avenue Louis Pasteur, Boston, MA 02115. E-mail: hweiner{at}rics.bwh.harvard.edu

Abbreviations: Ab, antibody; APC, antigen-presenting cell; EAE, experimental allergic encephalomyelitis; IL, interleukin; IFN, interferon; IPGTT, intraperitoneal glucose tolerance test; IV, intravenous; LAP, latency-associated peptide; mAb, monoclonal antibody; MAPC, immunomagnetic cell sorting; MLN, mesenteric lymph node; PE, phycoerythrin; PLN, pancreatic lymph node; STZ, streptozocin; TGF, transforming growth factor; Th, T-helper

Anti-CD3 monoclonal antibody (mAb) has been shown to induce tolerance and to be an effective treatment for diabetes both in animal models and in human trials. We have shown that anti-CD3 mAb given orally is biologically active in the gut and suppresses experimental autoimmune encephalitis by the induction of a regulatory T-cell that expresses latency-associated peptide (LAP) on its surface. In the present study, we investigated the effect of oral anti-CD3 mAb on the prevention of autoimmune diabetes in AKR mice in which the low-dose streptozocin (STZ) model induces autoimmunity to the ß-cells of the islets. We found that oral anti-CD3 mAb given at doses of 50 and 250 µg/feeding suppressed the incidence of diabetes in this model with the best effects seen at the 50 µg/dose. Associated with suppression, we observed decreased cell proliferation in the spleen and conversion of T-helper (Th)1 responses into Th2/Th3 responses in the periphery, including the pancreatic lymph nodes. Oral anti-CD3 mAb increased the expression of LAP on CD4⁺ T-cells, and these cells could adoptively transfer protection. Protection by oral anti-CD3 was transforming growth factor-ß dependent. Our results demonstrate that oral anti-CD3 is effective in the model of STZ-induced diabetes and may be a useful form of therapy for type 1 diabetes in humans.

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