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Clinical intervention trials evaluating the efficacy of antibody immunotherapy in type 1 diabetes are in progress. We tested effects on prediabetic islet antigen-specific autoreactive T cells of antithymocyte globulin (ATG) and humanized monoclonal antibodies against CD3 (ChAglyCD3) or CD25 (daclizumab) with regard to downmodulation of the target protein, proliferation, cytokine production, complement-dependent cytotoxicity (CDC), antibody-dependent cell cytotoxicity (ADCC), and survival. ATG leads to depletion of autoreactive CD4+ T cells by ADCC, CDC, and apoptosis, whereas anti-CD3 and anti-CD25 inhibited T-cell autoreactivity in a nondepleting fashion. ATG treatment led to a cytokine burst of Th1- and Th2-associated cytokines. Modulation of cytokine release through humanized monoclonal antibodies was moderate and selective: anti-CD25 led to increased release of IL-2 and reduced production of TNFalpha, whereas anti-CD3 decreased release of interferon-y and IL-5 and increased secretion of IL-10. ATG and the humanized monoclonal antibodies displayed contrasting mechanisms of action.

Original publication

DOI

10.1016/j.humimm.2006.02.027

Type

Journal article

Journal

Hum Immunol

Publication Date

04/2006

Volume

67

Pages

264 - 273

Keywords

Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antigens, CD3, Antilymphocyte Serum, Apoptosis, Cell Proliferation, Clone Cells, Cytokines, Diabetes Mellitus, Type 1, Glutamate Decarboxylase, Humans, Immunization, Passive, Immunoglobulin G, Isoenzymes, Lymphocyte Activation, T-Lymphocytes