Transgenic overexpression of human Bcl-2 in islet beta cells inhibits apoptosis but does not prevent autoimmune destruction
- Allison, J; Thomas, H; Beck, D; Brady, JL; Lew, AM; Elefanty, A; Kosaka, H; Kay, TW; Huang, DCS; Strasser, A;
Publication Year 2000-01, Volume 12, Issue #1, Page 9-17
- Journal Title
- INTERNATIONAL IMMUNOLOGY
- Publication Type
- Journal Article
- Insulin-dependent diabetes mellitus results when > 90% of the insulin-producing beta cells in the pancreatic islets are killed as a result of autoimmune attack by T cells. During the progression to diabetes, islet beta cells die as a result of different insults from the immune system, Agents such as perforin and granzymes, CD95 ligand and tumor necrosis factor-alpha, or cytokines and free-radicals have all been shown to cause beta 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 beta cells. Although Bcl-2 was able to prevent apoptosis induced by cytotoxic agents against beta cells in vitro, Bcl-2 alone could not prevent or ameliorate cytotoxic or autoimmune beta cell damage in vivo.
- OXFORD UNIV PRESS
- DEPENDENT DIABETES-MELLITUS; ANTI-FAS ANTIBODY; SELF-ANTIGENS; CYTOCHROME-C; CROSS-PRESENTATION; NITRIC-OXIDE; IFN-GAMMA; T-CELLS; DEATH; MICE
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2000-01-01 12:00:00Last Modified: 0001-01-01 12:00:00