Holz, Lauren E. and Benseler, Volker and Bowen, David G. and Bouillet, Philippe and Strasser, Andreas and O'Reilly, Lorraine and D'Avigdor, William M. H. and Bishop, Alex G. and McCaughan, Geoffrey W. and Bertolino, Patrick (2008) Intrahepatic murine CD8 T-Cell activation associates with a distinct phenotype leading to Bim-dependent death. GASTROENTEROLOGY, 135 (3). pp. 989-997. ISSN 0016-5085,
Full text not available from this repository. (Request a copy)Abstract
Background & Aims: Chronic infections by hepatotropic viruses such as hepatitis B and C are generally associated with an impaired CD8 T-cell immune response that is unable to clear the virus. The liver is increasingly recognized as an alternative site in which primary activation of CD8 T cells takes place, a property that might explain its role in inducing tolerance. However, the molecular mechanism by which intrahepatically activated T cells become tolerant is unknown. Here, we investigated the phenotype and fate of naive CD8 T cells activated by hepatocytes in vivo. Methods: Transgenic mouse models in which the antigen is expressed in lymph nodes and/or in the liver were adoptively transferred with naive CD8 T cells specific for the hepatic antigen. Results: Liver-activated CD8 T cells displayed poor effector functions and a unique CD25(low) CD54(low) phenotype. This phenotype was associated with increased expression of the proapoptotic protein Bim and caspase-3, demonstrating that these cells are programmed to die following intrahepatic activation. Importantly, we show that T cells deficient for Bim survived following intrahepatic activation. Conclusions: This study identifies Bim for the first time as a critical initiator of T-cell death in the liver. Thus, strategies inhibiting the up-regulation of this molecule could potentially be used to rescue CD8 T cells, clear the virus, and reverse the outcome of viral chronic infections affecting the liver.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHRONIC HEPATITIS-C; SELF-ANTIGEN; PERIPHERAL DELETION; CROSS-PRESENTATION; LIVER TOLERANCE; TRANSGENIC MICE; INFECTION; HEPATOCYTES; EXPRESSION; DIFFERENTIATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Oct 2020 07:59 |
| Last Modified: | 26 Oct 2020 07:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/30352 |
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