Diabetes, autoimmune

The first mouse monoclonal antibody specific for human CD3 was produced in 1979 and named orthoclone OKT3. Aside from its use in the laboratory, OKT3 became the first anti-CD3 antibody to be utilized in transplantation medicine, but its wider application was hampered by its immunogenic and mitogenic properties (reviewed in [6]). Consequently, humanized and engineered anti-CD3 antibodies were developed to circumvent these limitations (Table 1). Since T cells and the TCR are involved in many immunological diseases, it is not surprising that the application of CD3 antibodies is not restricted to the field of transplantation. For example, CD3 antibodies are tested in clinical studies of diseases such as autoimmune diabetes (type 1 diabetes), immune-mediated inflammatory arthritis and inflammatory bowel disease [7]. 

Singh B, Sharpe A, Bluestone JA B7/CD28 costimulation is essential for the homeostasis of the CD4-iCD25+ immunoregulatory T cells that control autoimmune diabetes. Immunity 2000 12 431-440. 

Guler, M.L. et al., Two autoimmune diabetes loci influencing T cell apoptosis control susceptibility to experimental autoimmune myocarditis, J. Immunol., 174, 2167, 2005. 

Graves, P.M., etal. Prospective study of enteroviral infections and development of beta-cell autoimmunity. Diabetes autoimmunity study in the young (DAISY), Diabetes Res. Clin. 

Carlsson, S., et al., Smoking is associated with an increased risk of type 2 diabetes but a decreased risk of autoimmune diabetes in adults an 11-year follow-up of incidence of diabetes in the Nord-Trondelag study, Diabetologia, 47, 1953, 2004. 

Herold, K.C. et al., Regulation of cytokine production during development of autoimmune diabetes induced with multiple low doses of streptozotocin. J. Immunol., 156,3521,1996. 

Others Acetazolamide Lithium Thiaazides Phenytoin Rash, fever, autoimmunity Dermatitis autoimmune thyroiditis, vasculitis Hypersensitivity, photosensitivity autoimmunity (diabetes) Rash drug-induced SLE, hepatitis... 

Tang Q, Henriksen KJ, Bi M, Finger EB, Szot G, Ye J, MasteUer EL, McDevitt H, Bonyhadi M, Bluestone JA In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes. J Exp Med 2004 199 1455-1465. 

Tarbell KV, Yamazaki S, Olson K, Toy P, Steinman RM CD25+CD4+ T cells, expanded with dendritic cells presenting a single autoantigenic peptide, suppress autoimmune diabetes. J Exp Med 2004 199 1467-1477. 

Chen Z, Herman AE, Matos M, Mathis D, Benoist C Where CD4+CD25 + Treg cells impinge on autoimmune diabetes. J Exp Med 2005 202 1387-1397. 

Bruder D, Westendorf AM, Hansen W, Prettin S, Gruber AD, Qian Y, von Bohmer H, Mahnke K, Buer J On the edge of autoimmunity T-cell stimulation by steady-state dendritic cells prevents autoimmune diabetes. Diabetes 2005 54 3395-3401. 

You S, Leforban B, Garcia C, Bach JF, Bluestone JA, Chatenoud L Adaptive TGF-p-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment. Proc Natl Acad Sd USA 2007 104 6335-6340. 

Hanninen A, Harrison LC "y8 T cells as mediators of mucosal tolerance the autoimmune diabetes model. Immunol Rev 2000 173 109-119. 

B3. Benoist, C., and Mathis, D., Cell death mediators in autoimmune diabetes—no shortage of suspects. Cell 89, 1-3 (1997). 

Two groups (Kaufman et al, 1993 Tisch et al., 1993) have shown that helper T-cell responses to GAD occur in a temporal fashion that coincides with the development of insulitis during the onset of diabetes in the NOD mouse. Also, interthymic injection of GAD65 prevents both T-cell proliferative response to GAD and the development of diabetes in the NOD mouse. These studies indicate that an immune response to GAD may play an important early role in the development of autoimmune diabetes. 

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