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

Zhang, Huang-Ge and Fleck, Martin and Kern, Earl R. and Liu, Di and Wang, Yongming and Hsu, Hui-Chen and Yang, Pingar and Wang, Zheng and Curiel, David T. and Zhou, Tong and Mountz, John D. (2000) Antigen presenting cells expressing Fas ligand down-modulate chronic inflammatory disease in Fas ligand-deficient mice. JOURNAL OF CLINICAL INVESTIGATION, 105 (6). pp. 813-821. ISSN 0021-9738

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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. PasL-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.

Item Type: Article
Uncontrolled Keywords: MARGINAL-ZONE MACROPHAGES; MURINE CYTOMEGALOVIRUS; LPR MICE; T-CELLS; APOPTOSIS; GENE; ACTIVATION; INDUCTION; INSERTION; TOLERANCE;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 31 May 2022 10:58
Last Modified: 31 May 2022 10:58
URI: https://pred.uni-regensburg.de/id/eprint/42789

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