Address for correspondence: Lisl K.M. Shoda, Ph.D., Entelos Inc., 110 Marsh Drive, Foster City, CA 94404. Voice: 650-572-5400; fax: 650-572-5401.
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Abstract

Abstract: Anti-CD3 antibody therapy, a promising clinical approach for the treatment of type 1 diabetes (T1D), was investigated using a mathematical model of T1D in the female nonobese diabetic (NOD) mouse. Analyses of model simulation results indicate that, in addition to the known direct effects of anti-CD3 antibody on T lymphocytes, two additional mechanisms are required for sustained disease remission: (a) rapid regrowth of healthy β cells following clearance of islet inflammation and (b) enhanced regulatory T cell activity and/or phenotypic changes in antigen presenting cells (APCs) that promote a stable regulatory environment in the pancreas.

REFERENCES

1 Herold, K.C., S.E. Gitelman, U. Masharani, et al . 2005. A single course of anti-CD3 monoclonal antibody hOKT3{gamma}1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes. Diabetes 54: 1763–1769.
10.2337/diabetes.54.6.1763
CASPubMedWeb of Science®Google Scholar
2 Keymeulen, B., E. Vandemeulebroucke, A.G. Ziegler, et al . 2005. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N. Engl. J. Med. 352: 2598–2608.
10.1056/NEJMoa043980
CASPubMedWeb of Science®Google Scholar
3 Belghith, M., J.A. Bluestone, S. Barriot, et al . 2003. TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes. Nat. Med. 9: 1202–1208.
10.1038/nm924
CASPubMedWeb of Science®Google Scholar
4 Hayward, A.R. & M. Shreiber. 1989. Neonatal injection of CD3 antibody into nonobese diabetic mice reduces the incidence of insulitis and diabetes. J. Immunol. 143: 1555–1559.
CASPubMedWeb of Science®Google Scholar
5 Shoda, L.K., D.L. Young, S. Ramanujan, et al . 2005. A comprehensive review of interventions in the NOD mouse and implications for translation. Immunity 23: 115–126.
10.1016/j.immuni.2005.08.002
CASPubMedWeb of Science®Google Scholar
6 Chatenoud, L., E. Thervet, J. Primo & J.F. Bach. 1994. Anti-CD3 antibody induces long-term remission of overt autoimmunity in nonobese diabetic mice. Proc. Natl. Acad. Sci. USA 91: 123–127.
10.1073/pnas.91.1.123
CASPubMedWeb of Science®Google Scholar
7 Chatenoud, L., J. Primo & J.F. Bach. 1997. CD3 antibody-induced dominant self tolerance in overtly diabetic NOD mice. J. Immunol. 158: 2947–2954.
10.4049/jimmunol.158.6.2947
CASPubMedWeb of Science®Google Scholar
8 Ruprecht, C.R., M. Gattorno, F. Ferlito, et al . 2005. Coexpression of CD25 and CD27 identifies FoxP3⁺ regulatory T cells in inflamed synovia. J. Exp. Med. 201: 1793–1803.
10.1084/jem.20050085
CASPubMedWeb of Science®Google Scholar

Citing Literature

Volume1079, Issue1

Immunology of Diabetes IV: Progress in Our Understanding

October 2006

Pages 369-373

Mechanisms Mediating Anti-CD3 Antibody Efficacy

Insights from a Mathematical Model of Type 1 Diabetes

Abstract

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Mechanisms Mediating Anti-CD3 Antibody Efficacy

Insights from a Mathematical Model of Type 1 Diabetes

Abstract

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Citing Literature

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