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

被引:50
作者
Zhang, HG
Fleck, M
Kern, ER
Liu, D
Wang, YM
Hsu, HC
Yang, PG
Wang, Z
Curiel, DT
Zhou, T
Mountz, JD
机构
[1] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA
[2] Univ Regensburg, Dept Med, D-8400 Regensburg, Germany
[3] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA
[4] Univ Alabama Birmingham, Gene Therapy Program, Birmingham, AL 35294 USA
[5] Vet Adm Med Ctr, Birmingham, AL 35233 USA
关键词
D O I
10.1172/JCI8236
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:813 / 821
页数:9
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