MMPs are required for recruitment of antigen-nonspecific mononuclear cells into the liver by CTLs

被引:103
作者
Sitia, G
Isogawa, M
Iannacone, M
Campbell, IL
Chisari, FV
Guidotti, LG
机构
[1] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA
[2] Ist Sci San Raffaele, Dept Infect Dis, I-20132 Milan, Italy
[3] Ist Sci San Raffaele, Dept Internal Med, I-20132 Milan, Italy
[4] Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA
关键词
D O I
10.1172/JCI200421087
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 recently showed that andgen-nonspecific inflammatory cells are recruited into the liver when hepatitis B virus (HBV)-specific CTLs are injected into HBV transgenic mice, and that this process amplifies the severity of liver disease. We also showed that the severity of CTL-induced liver disease is ameliorated by the depletion of Gr-1(+) cells (Gr-1 is an antigen highly expressed by neutrophils), which, secondarily, abolishes the intrahepatic recruitment of all andgen-nonspecific Gr-1(-) mononuclear cells (NK and NKT cells, T and B lymphocytes, monocytes, macrophages, dendritic cells) despite the strong induction of chemokine gene expression. Those results suggested that in addition to chemokine expression, CTL-induced functions are necessary for mononuclear cell recruitment to occur. We now report that MMPs known to be produced by Gr-1(+) cells are rapidly induced in the livers of CTL-injected mice. The inhibition of MMP activity reduced the intrahepatic recruitment of andgen-nonspecific mononuclear cells and much of the attending liver disease without affecting the migration or antiviral potential of antigen-specific CTLs. The notion that the inhibition of MMP activity is associated with maintenance of antiviral effects but diminished tissue damage may be significant for the development of immunotherapeutic approaches for the treatment of chronic HBV infection.
引用
收藏
页码:1158 / 1167
页数:10
相关论文
共 38 条
  • [1] MECHANISMS OF CLASS-I RESTRICTED IMMUNOPATHOLOGY - A TRANSGENIC MOUSE MODEL OF FULMINANT-HEPATITIS
    ANDO, K
    MORIYAMA, T
    GUIDOTTI, LG
    WIRTH, S
    SCHREIBER, RD
    SCHLICHT, HJ
    HUANG, SN
    CHISARI, FV
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1993, 178 (05) : 1541 - 1554
  • [2] ANDO K, 1994, J IMMUNOL, V152, P3245
  • [3] Metalloproteinase inhibitors: biological actions and therapeutic opportunities
    Baker, AH
    Edwards, DR
    Murphy, G
    [J]. JOURNAL OF CELL SCIENCE, 2002, 115 (19) : 3719 - 3727
  • [4] Protection or damage: a dual role for the virus-specific cytotoxic T lymphocyte response in hepatitis B and C infection?
    Bertoletti, A
    Maini, MK
    [J]. CURRENT OPINION IN IMMUNOLOGY, 2000, 12 (04) : 403 - 408
  • [5] Identification of a CD11b+/Gr-1+/CD31+ myeloid progenitor capable of activating or suppressing CD8+ T cells
    Bronte, V
    Apolloni, E
    Cabrelle, A
    Ronca, R
    Serafini, P
    Zamboni, P
    Restifo, NP
    Zanovello, P
    [J]. BLOOD, 2000, 96 (12) : 3838 - 3846
  • [6] Matrix metalloproteinase-9 deficiency impairs cellular infiltration and bronchial hyperresponsiveness during allergen-induced airway inflammation
    Cataldo, DD
    Tournoy, KG
    Vermaelen, K
    Munaut, C
    Foidart, JM
    Louis, R
    Noël, A
    Pauwels, RA
    [J]. AMERICAN JOURNAL OF PATHOLOGY, 2002, 161 (02) : 491 - 498
  • [7] CHISARI FV, 1995, ANNU REV IMMUNOL, V13, P29, DOI 10.1146/annurev.iy.13.040195.000333
  • [8] Dendritic cell responses to early murine cytomegalovirus infection:: Subset functional specialization and differential regulation by interferon α/β
    Dalod, M
    Hamilton, T
    Salomon, R
    Salazar-Mather, TP
    Henry, SC
    Hamilton, JD
    Biron, CA
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (07) : 885 - 898
  • [9] HIGH-LEVEL HEPATITIS-B VIRUS-REPLICATION IN TRANSGENIC MICE
    GUIDOTTI, LG
    MATZKE, B
    SCHALLER, H
    CHISARI, FV
    [J]. JOURNAL OF VIROLOGY, 1995, 69 (10) : 6158 - 6169
  • [10] Viral cross talk: Intracellular inactivation of the hepatitis B virus during an unrelated viral infection of the liver
    Guidotti, LG
    Borrow, P
    Hobbs, MV
    Matzke, B
    Gresser, I
    Oldstone, MBA
    Chisari, FV
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (10) : 4589 - 4594