Antigen presenting cells expressing Fas ligand down-modulate chronic inflammatory disease in Fas ligand–deficient mice
Huang-Ge Zhang, … , Tong Zhou, John D. Mountz
Huang-Ge Zhang, … , Tong Zhou, John D. Mountz
Published March 15, 2000
Citation Information: J Clin Invest. 2000;105(6):813-821. https://doi.org/10.1172/JCI8236.
View: Text | PDF
Article

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

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

×

Figure 5

Options: View larger image (or click on image) Download as PowerPoint
Less-severe inflammation in the lung, kidney, and liver of APC-AdFasL–tr...
Less-severe inflammation in the lung, kidney, and liver of APC-AdFasL–treated MCMV-infected B6-gld/gld mice. B6-gld/gld and B6-lpr/lpr mice were treated with either APC-AdCMVLacZ (control), MCMV-infected APC (APC+MCMV), APC-AdFasL, or APC-AdFasL+MCMV beginning 28 days after MCMV infection. The mice were treated every 3 days with 4 doses and analyzed 4 weeks after initiation of APC therapy. There were at least 5 mice in each treatment group. The lung, kidney, and liver were stained for H&E and scored by 3 blinded investigators. The histology score was as described in Figure 2. At least 10 fields of view were analyzed for each organ of each mice. The bar graph represents the mean ± SEM of the inflammatory scores from each organ for mice underlying the indicated treatment. *P < 0.05, compared with control treatment group.