Liver Damage by Infiltrating CD8+ T Cells Is Fas Dependent

• Published in: The Journal of immunology (1950) Vol. 167; no. 11; pp. 6654 - 6662
• Main Authors: Kennedy, Norman J, Russell, Jennifer Q, Michail, Nina, Budd, Ralph C
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.12.2001
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Cell Death - immunology; Cell Movement - immunology; Cytotoxicity, Immunologic - immunology; Egg Proteins - administration & dosage; Egg Proteins - immunology; fas Receptor - physiology; fas Receptor - toxicity; Female; Hepatocytes - immunology; Hepatocytes - pathology; Immunophenotyping; Injections, Intraperitoneal; Liver - immunology; Liver - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Inbred MRL lpr; Mice, Transgenic; Ovalbumin - administration & dosage; Ovalbumin - immunology; Peptide Fragments - administration & dosage; Peptide Fragments - immunology; Species Specificity; Tumor Cells, Cultured
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.167.11.6654

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.