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Rev Diabet Stud, 2012, 9(2-3):68-81 DOI 10.1900/RDS.2012.9.68

Immunotherapy in Autoimmune Type 1 Diabetes

Benno Weigmann1, Randi K. Franke2, Carolin Daniel2

1Research Campus of the Friedrich-Alexander University Erlangen-Nuernberg, Medical Clinic I, 91052 Erlangen, Germany
2Helmholtz Zentrum Muenchen - German Center on Environmental Health, Institute of Diabetes Research 1, Junior Group Immunological Tolerance in Type 1 Diabetes, Ingolstaedter Landstrasse 1, Neuherberg, 85764 Munich, Germany
Address correspondence to: Carolin Daniel, e-mail: carolin.daniel@helmholtz-muenchen.de

Manuscript submitted October 18, 2012; resubmitted November 3, 2012; accepted November 7, 2012.

Keywords: Immunotherapy, autoimmunity, type 1 diabetes, insulin, regulatory T cells, Foxp3, mimetope, antigen, tolerance, suppression

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disease affecting millions of people worldwide. The disease is characterized by the loss of self-tolerance to the insulin-producing β-cells in the pancreas, the destruction of β-cells, and finally the development of chronic hyperglycemia at diagnosis of T1D. Its incidence and prevalence are rising dramatically, highlighting the need for immunotherapeutic strategies able to prevent or treat the disease in a safe and specific manner. Immunotherapeutic strategies are being developed, and aim to restore immunological self-tolerance, thereby limiting unwanted immunity and β-cell destruction. Foxp3+ regulatory T (Treg) cells exert essential functions to maintain and restore immunological self-tolerance. The identification of the transcription factor Foxp3 as the specification factor for the Treg cell lineage facilitated our understanding in the biology of Treg generation and function. This review highlights the current understanding of immunotherapeutic approaches as preventative and curative measures for autoimmune T1D. It includes an overview on early immunointervention studies, which made use of general immunosuppressive agents such as cyclosporin A, followed by a discussion on newly emerging clinical trials. Besides non-antigen-specific therapies, particular attention is given to antigen-specific generation of Foxp3+ Treg cells and their potential use to limit autoimmunity such as T1D.

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