Elimanation of activated but not resting primary human CD4+ and CD8+ T cells by Fas ligand (FasL/Cd95L)-expressing Killer-dendritic cells

Academic Article


  • Dendritic cells (DC) genetically engineered to express high levels of Fas ligand (FasL/CD95L) have been demonstrated to delete T cells in an antigen specific manner in several different animal models in vivo. However, the immunomodulatory capacity of primary human FasL-expressing Killer-DC has not been determined. Therefore, human Killer-DC were generated from mature monocyte-derived DC using the inducible CRE/LoxP adenoviral vector system, and the immunoregulatory capacity of these cells was analyzed in cocultures with primary human T cells in vitro. Combined transductions of DC by AdloxPFasL and AxCANCre resulted in FasL expression in > 70% of DC without affecting the mature phenotype. Proliferation of activated primary human T cells was inhibited up to 80% in cocultures with FasL-expressing DC but not EGFP-transduced DC, which was due to induction of apoptosis in activated but not resting CD4+ and CD8+ T cells. Apoptosis induced by Killer-DC could be blocked by an anti-FasL-antibody in a dose dependent fashion. The present results demonstrate that FasL-expressing Killer-DC eliminate activated but not resting primary human CD4+ and CD8+ T cells by induction of Fas-mediated apoptosis supporting the concept to apply Killer-DC as a novel strategy for the treatment of T cell-dependent autoimmune disease and allograft rejection in humans.
  • Published In

  • Immunobiology  Journal
  • Digital Object Identifier (doi)

    Author List

  • Hoves S; Krause SW; Herfarth H; Halbritter D; Zhang HG; Mountz JD; Schölmerich J; Fleck M
  • Start Page

  • 463
  • End Page

  • 475
  • Volume

  • 208
  • Issue

  • 5