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Prevention of autoimmune diabetes mellitus in NOD mice by transgenic expression of soluble tumor necrosis factor receptor p55

Hunger, R. E.
Carnaud, C.
Published in European Journal of Immunology. 1997, vol. 27, no. 1, p. 255-261
Abstract The non-obese diabetic (NOD) mouse represents a relevant animal model of autoimmunity for insulin-dependent diabetes mellitus. The pathogenic role of tumor necrosis factor (TNF) in insulitis and beta cell destruction observed in these mice remains controversial, since injections of TNF or of anti-TNF antibodies have been reported to exert protection or acceleration of diabetes, depending on the timing of administration. In this study, we demonstrate that, in contrast to the non-transgenic littermates, NOD mice with permanent neutralization of TNF by high blood levels of soluble TNF receptor p55-human FcIgG3-fusion molecules resulting from the expression of a transgene are protected from spontaneous diabetes. They are also protected from accelerated forms of disease caused by transfer of NOD spleen cells or cyclophosphamide injections. This protection is associated with a marked decrease in the severity and incidence of insulitis and in the expression of the adhesion molecules MAdCAM-1 and ICAM-1 on the venules of pancreatic islets. These data suggest a central role for TNF-alpha in the mediation of insulitis and of the subsequent destruction of insulin-secreting beta-cells observed in NOD mice. They may be relevant to cell-mediated autoimmune diseases in general, in which treatment with soluble TNF receptors might be beneficial.
Keywords AnimalsDiabetes Mellitus, Type 1/pathology/*prevention & controlIslets of Langerhans/pathologyMiceMice, Inbred NOD/*immunologyMice, TransgenicReceptors, Tumor Necrosis Factor/*chemistry/physiologySolubilityTumor Necrosis Factor-alpha/*antagonists & inhibitors
PMID: 9022027
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HUNGER, R. E. et al. Prevention of autoimmune diabetes mellitus in NOD mice by transgenic expression of soluble tumor necrosis factor receptor p55. In: European Journal of Immunology, 1997, vol. 27, n° 1, p. 255-261. doi: 10.1002/eji.1830270138 https://archive-ouverte.unige.ch/unige:11047

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Deposited on : 2010-08-27

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