Antigen presenting cells expressing Fas ligand down-modulate chronic inflammatory disease in Fas ligand-deficient mice

J Clin Invest. 2000 Mar;105(6):813-21. doi: 10.1172/JCI8236.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Antigen-Presenting Cells / immunology*
  • Antigen-Presenting Cells / transplantation
  • Apoptosis*
  • Autoantibodies / biosynthesis
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / therapy
  • Fas Ligand Protein
  • Female
  • Genetic Vectors / genetics
  • Hepatitis, Viral, Animal / etiology
  • Hepatitis, Viral, Animal / immunology
  • Hepatitis, Viral, Animal / pathology
  • Inflammation
  • Kidney / pathology
  • Liver / pathology
  • Lung / pathology
  • Lung Diseases, Interstitial / etiology
  • Lung Diseases, Interstitial / immunology
  • Lung Diseases, Interstitial / pathology
  • Macrophages / immunology
  • Membrane Glycoproteins / deficiency
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred MRL lpr
  • Mice, Mutant Strains
  • Nephritis / etiology
  • Nephritis / immunology
  • Nephritis / pathology
  • Specific Pathogen-Free Organisms
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocyte Subsets / immunology
  • Transfection
  • fas Receptor / physiology


  • Autoantibodies
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • fas Receptor