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Publication : Liver damage by infiltrating CD8+ T cells is Fas dependent.

First Author  Kennedy NJ Year  2001
Journal  J Immunol Volume  167
Issue  11 Pages  6654-62
PubMed ID  11714837 Mgi Jnum  J:72817
Mgi Id  MGI:2153640 Doi  10.4049/jimmunol.167.11.6654
Citation  Kennedy NJ, et al. (2001) Liver damage by infiltrating CD8(+) T cells is fas dependent. J Immunol 167(11):6654-62
abstractText  Ag stimulation of CD8(+) lymphocytes in vivo results in their migration to various tissues as well as the activation of a cytolytic program involving perforin, TNF-alpha, and Fas ligand. The liver is one of the main sites for infiltration by activated CD8(+) T cells, and this is followed by the death of hepatocytes. The contribution of the various cytolytic components to this process is unclear. Hepatocyte damage by CD8(+) T cells was studied using the MHC class I-restricted OVA-specific TCR transgenic mouse (OT-1) to examine the contribution of Fas to hepatocyte death. Activated CD8(+) T cells from both OT-1 and Fas-deficient OT-1lpr mice migrated to the liver in similar numbers after OVA administration, but only in OT-1 mice was there evidence of significant hepatocyte damage histologically and by elevation of serum aspartate transaminase. These differences were not the result of inefficient induction of cytolytic activity in OT-1lpr liver T cells, since they were as cytolytic in vitro as OT-1 liver T cells. This was supported by findings of similar high levels of message for perforin, TNF-alpha, and Fas ligand in liver lymphocytes from both mice. These findings demonstrate that following Ag activation, infiltrating liver CD8(+) T lymphocytes induce hepatocyte damage in a Fas-dependent manner.
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