title: Antigen presenting cells expressing Fas ligand down-modulate chronic inflammatory disease in Fas ligand-deficient mice.
abstract: We assessed the effect of modified antigen presenting cells (APCs) expressing high levels of Fas ligand (APC-FasL) on post-viral chronic inflammatory disease. FasL-deficient B6-gld/gld mice infected with murine cytomegalovirus (MCMV) cleared the virus from their lungs, kidneys, and livers within 2 weeks of infection. However, inflammation persisted in these organs for more than 8 weeks, with a chronically increased T-cell response to MCMV-infected APCs and production of autoantibodies. Administration of APC-AdFasL at 4 weeks suppressed this inflammation and diminished the T-cell response and autoantibody production. APC-AdFasL that had been transfected with ultraviolet-irradiated MCMV were more effective than uninfected APC-AdFasL in ameliorating the chronic inflammation. APC-AdFasL migrated preferentially to the spleen, where they triggered apoptosis of lymphocytes in the marginal zone of the spleen. These results confirm that Fas-mediated apoptosis is not required for clearance of virus, but is required for down-modulation of the virally induced chronic inflammatory response. This organwide effect of APC-AdFasL appears to be mediated by elimination of activated T lymphocytes in the spleen before their emigration to the target organs.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama-Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: H G
authors.initials: HG
authors.lastname: Zhang
authors.forename: M
authors.initials: M
authors.lastname: Fleck
authors.forename: E R
authors.initials: ER
authors.lastname: Kern
authors.forename: D
authors.initials: D
authors.lastname: Liu
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: H C
authors.initials: HC
authors.lastname: Hsu
authors.forename: P
authors.initials: P
authors.lastname: Yang
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.forename: D T
authors.initials: DT
authors.lastname: Curiel
authors.forename: T
authors.initials: T
authors.lastname: Zhou
authors.forename: J D
authors.initials: JD
authors.lastname: Mountz
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000637:transplantation; D017209:Apoptosis; D001323:Autoantibodies / Q000096:biosynthesis; D003586:Cytomegalovirus Infections / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D053222:Fas Ligand Protein; D005260:Female; D005822:Genetic Vectors / Q000235:genetics; D006524:Hepatitis, Viral, Animal / Q000209:etiology / Q000276:immunology / Q000473:pathology; D007249:Inflammation; D007668:Kidney / Q000473:pathology; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000209:etiology / Q000276:immunology / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019463:Mice, Inbred MRL lpr; D008817:Mice, Mutant Strains; D009393:Nephritis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000276:immunology / Q000473:pathology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014162:Transfection; D019014:fas Receptor / Q000502:physiology
chemical_list: D001323:Autoantibodies; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D019014:fas Receptor