Abstract
We identified a novel mechanism by which CD8 T cells selectively eliminate virus-infected hepatocytes without direct MHC class I recognition. This mechanism involves TNF secreted by CD8 T cells, which selectively induces death of infected hepatocytes. Triggering of the TNF receptor can induce both, pro-survival pathways via NFkB activation, and apoptotic pathways involving generation of ROS and caspase activation. The molecular mechanisms directing into one or the other pathway are still unknown. However, in virus-infected hepatocytes stimulation of the TNF receptor induces apoptotic pathways, whereas uninfected hepatocytes survive. Here, we investigate the molecular mechanism(s) underlying the sensitization of infected hepatocytes towards the apoptosis-inducing effect of TNF.
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