Localization of Fas ligand in cytoplasmic granules of CD8+ cytotoxic T lymphocytes and natural killer cells: participation of Fas ligand in granule exocytosis model of cytotoxicity

Biochem Biophys Res Commun. 2002 Aug 16;296(2):328-36. doi: 10.1016/s0006-291x(02)00841-0.


Fas ligand (FasL) has been implicated in cytotoxic T lymphocyte (CTL)- and natural killer (NK) cell-mediated cytotoxicity. In the present study, we investigated the localization of FasL in murine CTL and NK cells. Immunocytochemical staining showed that FasL was stored in cytoplasmic granules of CD8+ CTL clones and in vivo activated CTL and NK cells, where perforin and granzyme A also resided. Immunoelectron microscopy revealed that FasL was localized on outer membrane of the cytoplasmic granules, while perforin was localized in internal vesicles. Western blot analysis showed that the membrane-type FasL of 40 kDa was stored in CD8+ CTL clones but not in CD4+ CTL clones. By utilizing a granule exocytosis inhibitor (TN16), we demonstrated that FasL translocated onto cell surface upon degranulation of anti-CD3-stimulated CD8+ CTL clones. Moreover, TN16 markedly inhibited the FasL-mediated cytotoxicity by CD8+ T cell clones and NK cells. These results suggested a substantial contribution of FasL to granule exocytosis-mediated target cell lysis by CD8+ CTL and NK cells.

MeSH terms

  • Animals
  • Antigens, Surface / immunology
  • Antigens, Surface / metabolism
  • Cells, Cultured
  • Cytoplasmic Granules / chemistry
  • Cytoplasmic Granules / metabolism*
  • Cytotoxicity, Immunologic*
  • Exocytosis*
  • Fas Ligand Protein
  • Flow Cytometry
  • Humans
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology
  • Killer Cells, Natural / metabolism*
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • Pyrrolidinones / metabolism
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / metabolism*


  • Antigens, Surface
  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Pyrrolidinones
  • Perforin
  • TN 16