Hoves, Sabine and Krause, Stefan W. and Herfarth, Hans and Halbritter, Dagmar and Zhang, Huang-Ge and Mountz, John D. and Schoelmerich, Juergen and Fleck, Martin (2004) Elimination of activated but not resting primary human CD4(+) and CD8(+) T cells by Fas ligand (FasL/CD95L)-expressing Killer-dendritic cells. IMMUNOBIOLOGY, 208 (5). pp. 463-475. ISSN 0171-2985
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTIGEN-PRESENTING CELLS; HUMAN PERIPHERAL-BLOOD; IN-VIVO; COSTIMULATORY SIGNALS; STIMULATORY CAPACITY; MEDIATED APOPTOSIS; IMMUNE-SYSTEM; GENE-TRANSFER; MURINE MODEL; DEATH; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Aug 2021 08:30 |
| Last Modified: | 04 Aug 2021 08:30 |
| URI: | https://pred.uni-regensburg.de/id/eprint/38165 |
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