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Immunobiology Program, Department of Medicine, University of Vermont College of Medicine, Burlington, VT 05405
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-
, 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-, 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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