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
相关论文
共 34 条
  • [11] 2-I
  • [12] FUKUNAGA RW, 1992, NATURE, V356, P314
  • [13] T-CELLS IN MULTIPLE-SCLEROSIS AND INFLAMMATORY CENTRAL NERVOUS-SYSTEM DISEASES
    HAFLER, DA
    WEINER, HL
    [J]. IMMUNOLOGICAL REVIEWS, 1987, 100 : 307 - 332
  • [14] FAS(CD95) FASL INTERACTIONS REQUIRED FOR PROGRAMMED CELL-DEATH AFTER T-CELL ACTIVATION
    JU, ST
    PANKA, DJ
    CUI, HL
    ETTINGER, R
    ELKHATIB, M
    SHERR, DH
    STANGER, BZ
    MARSHAKROTHSTEIN, A
    [J]. NATURE, 1995, 373 (6513) : 444 - 448
  • [15] Differential induction of apoptosis by Fas-Fas ligand interactions in human monocytes and macrophages
    Kiener, PA
    Davis, PM
    Starling, GC
    Mehlin, C
    Klebanoff, SJ
    Ledbetter, JA
    Liles, WC
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (08) : 1511 - 1516
  • [16] Long-term amelioration of rat adjuvant arthritis following systemic elimination of macrophages by clodronate-containing liposomes
    Kinne, RW
    SchmidtWeber, CB
    Hoppe, R
    Buchner, E
    PalomboKinne, E
    Nurnberg, E
    Emmrich, F
    [J]. ARTHRITIS AND RHEUMATISM, 1995, 38 (12): : 1777 - 1790
  • [17] Fas and the art of lymphocyte maintenance
    Lenardo, MJ
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (03) : 721 - 724
  • [18] THE MOUSE FAS-LIGAND GENE IS MUTATED IN GLD MICE AND IS PART OF A TNF FAMILY GENE-CLUSTER
    LYNCH, DH
    WATSON, ML
    ALDERSON, MR
    BAUM, PR
    MILLER, RE
    TOUGH, T
    GIBSON, M
    DAVISSMITH, T
    SMITH, CA
    HUNTER, K
    BHAT, D
    DIN, W
    GOODWIN, RG
    SELDIN, MF
    [J]. IMMUNITY, 1994, 1 (02) : 131 - 136
  • [19] ARE MURINE MARGINAL-ZONE MACROPHAGES THE SPLENIC WHITE PULP ANALOG OF HIGH ENDOTHELIAL VENULES
    LYONS, AB
    PARISH, CR
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1995, 25 (11) : 3165 - 3172
  • [20] Martin F, 1999, CURR TOP MICROBIOL, V246, P45