Home > Publications > Intrahepatic murine CD8 T cell activation associates with a distinct phenotype leading to Bim-dependent death
Centenary Institute - Medical Research
Centenary Institute - Medical Research

Intrahepatic murine CD8 T cell activation associates with a distinct phenotype leading to Bim-dependent death

BACKGROUND & AIMS:

Chronic infections by hepatotropic viruses such as hepatitis B and C are generally associated with an impaired CD8 T-cellimmune 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 naïve 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 naïveCD8 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 followingintrahepatic 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 li

Holz L.E., Benseler V., Bowen D.G., Bouillet P., Strasser A., O’Reilly L., d’Avigdor WMH, Bishop A.G., McCaughan G.W. and Bertolino P.

Gastroenterology 135, 135:989-997 (IF: 12.0) (2008)

Date: 2008

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