Fas-mediated apoptosis causes elimination of virus-specific cytotoxic T cells in the virus-infected liver.
Immunity to allogeneic MHC Ags is weak in rodent livers, raising questions as to the mechanisms that might control responses in this organ. Infection with an adenovirus vector reveals that T cell-mediated immunity to nonself-Ags in the liver is self-limiting. Virus-induced liver injury decreases and coincides with disappearance of virus-specific CTL, concomitant to an increase of apoptotic T cells early after infection. But whereas death in CD4 cells is independent of Fas, perforin, and TNF-alpha, that of CD8 cells requires Fas and not perforin or TNF-alpha pathways. Fas ligand is expressed on liver-infiltrating cells, pointing to death by fratricide that causes almost complete disappearance of virus-specific CTL 4 wk after infection. CTL elimination is virus dose dependent, and high doses induced high alanine aminotransferase values, elevated expression of Fas ligand on CD8 cells, and increased CD8 cell migration into the infected liver.
Liu
Z X
ZX
Department of Molecular Microbiology and Immunology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine at University of Southern California, Los Angeles, CA 90089, USA.
Govindarajan
S
S
Okamoto
S
S
Dennert
G
G
D000257:Adenoviridae Infections / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D017637:Clonal Deletion; D004306:Dose-Response Relationship, Immunologic; D053222:Fas Ligand Protein; D005260:Female; D006131:Growth Inhibitors / Q000494:pharmacology; D006520:Hepatitis, Animal / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D008024:Ligands; D008212:Lymphocyte Depletion; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D015398:Signal Transduction / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D019014:fas Receptor / Q000378:metabolism / Q000502:physiology*
D000956:Antigens, Viral; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D006131:Growth Inhibitors; D007376:Interleukin-2; D008024:Ligands; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor; D054353:Perforin