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Department of Molecular Microbiology and Immunology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90089
NK cells are a relatively rare cell population in peripheral
lymphoid organs but are abundant in the liver, raising questions as to
their function in immune responses to infections of this organ. To
investigate this, cell-mediated immunity to viral liver infection
induced by a type 5, replication-defective, adenovirus was examined. It
is shown that NK cells in the absence of T cells cause hepatocyte
apoptosis in virus-infected livers associated with an increase in liver
enzymes in the serum. Concomitantly, NK cells induce production of
IFN-
, inhibitable by their elimination before infection. NK cells
are shown to be necessary for optimal priming of virus-specific T
cells, assessed by delayed-type hypersensitivity response and CTL
activity, consistent with their ability to secrete IFN-. The
conclusion is drawn that NK cells mediate two important functions in
the liver: they induce cell death in the infected organ and
concomitantly stimulate the induction of T cell-mediated immunity by
release of IFN-.
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