International Immunology, Vol. 12, No. 1, 9-17,
January 2000
© 2000 Japanese Society for Immunology
Transgenic overexpression of human Bcl-2 in islet ß cells inhibits apoptosis but does not prevent autoimmune destruction
The Walter and Eliza Hall Institute for Medical Research, Post Office, Royal Melbourne Hospital, Victoria 3050, Australia
1 Department of Dermatology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565, Japan
Correspondence to: J. Allison
Insulin-dependent diabetes mellitus results when > 90% of the insulin-producing ß cells in the pancreatic islets are killed as a result of autoimmune attack by T cells. During the progression to diabetes, islet ß cells die as a result of different insults from the immune system. Agents such as perforin and granzymes, CD95 ligand and tumor necrosis factor-
, or cytokines and free-radicals have all been shown to cause ß cell apoptosis. The anti-apoptotic protein, Bcl-2, might protect against some of these stimuli. We have therefore generated transgenic mice expressing human Bcl-2 in their islet ß cells. Although Bcl-2 was able to prevent apoptosis induced by cytotoxic agents against ß cells in vitro, Bcl-2 alone could not prevent or ameliorate cytotoxic or autoimmune ß cell damage in vivo.
Keywords: ß cell death, insulin-dependent diabetes mellitus, non-obese diabetic mouse
Transmitting editor: M. Feldmann
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