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

Huang Ge Zhang, Martin Fleck, Earl R. Kern, Di Liu, Yongming Wang, Hui Chen Hsu, Pingar Yang, Zheng Wang, David T. Curiel, Tong Zhou, John D. Mountz

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

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.

Original languageEnglish
Pages (from-to)813-821
Number of pages9
JournalJournal of Clinical Investigation
Volume105
Issue number6
DOIs
StatePublished - Mar 2000

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