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.
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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

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Quantitative analysis of inflammation in the lung, kidney, and liver. B6...
Quantitative analysis of inflammation in the lung, kidney, and liver. B6+/+ and B6-gld/gld mice were infected intraperitoneally with MCMV (1 × 105 pfu) and lung (top panel), kidney (middle panel), and liver (bottom panel) tissues were assessed for severity of inflammation and tissue damage on a relative scale ranging from 0 (not present) to 4 (most severe). The bar graph represents the score ± SEM of at least 5 mice analyzed at each time point.