Elimination of activated but not resting primary human CD4⁺ and CD8⁺ T cells by Fas ligand (FasL/CD95L)-expressing Killer-dendritic cells

Authors: Hoves S.¹; Krause S.W.²; Herfarth H.¹; Halbritter D.¹; Zhang H-G.³; Mountz J.D.³; Schölmerich J.¹; Fleck M.¹

Source: Immunobiology, Volume 208, Number 5, March 2004 , pp. 463-475(13)

Publisher: Urban & Fischer

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Abstract:

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.

Document Type: Research article

DOI: http://dx.doi.org/10.1078/0171-2985-00293

Affiliations: 1: The University of Regensburg, Department of Internal Medicine I, 93042 Regensburg, Germany 2: The University of Regensburg, Department of Internal Medicine I, Division of Hematology and Oncology, 93042 Regensburg, Germany 3: The University of Alabama at Birmingham, Department of Medicine, Division of Clinical Immunology and Rheumatology, Birmingham, Alabama 35294, USA

Publication date: 2004-03-01