NK cells cause liver injury and facilitate the induction of T cell-mediated immunity to a viral liver infection.
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-gamma, 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-gamma. 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-gamma.
Liu
Z X
ZX
Department of Molecular Microbiology and Immunology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles 90089, USA.
Govindarajan
S
S
Okamoto
S
S
Dennert
G
G
D000257:Adenoviridae Infections / Q000276:immunology* / Q000473:pathology; D000818:Animals; D000941:Antigens / Q000096:biosynthesis / Q000276:immunology; D000954:Antigens, Surface; D005260:Female; D005677:G(M1) Ganglioside / Q000096:biosynthesis / Q000276:immunology; D006520:Hepatitis, Animal / Q000276:immunology* / Q000473:pathology; D007371:Interferon-gamma / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D055651:NK Cell Lectin-Like Receptor Subfamily B; D014176:Protein Biosynthesis; D011506:Proteins / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000821:virology
D000941:Antigens; D000954:Antigens, Surface; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D007371:Interferon-gamma