Schuetz, Christian and Hoves, Sabine and Halbritter, Dagmar and Zhang, Huang-Ge and Mountz, John D. and Fleck, Martin (2011) Alloantigen specific deletion of primary human T cells by Fas ligand (CD95L)-transduced monocyte-derived killer-dendritic cells. IMMUNOLOGY, 133 (1). pp. 115-122. ISSN 0019-2805, 1365-2567
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P>Numerous studies have been performed in vitro and in various animal models to modulate the interaction of dendritic cells (DC) and T cells by Fas (CD95/Apo-1) signalling to delete activated T cells via induction of activation-induced cell death (AICD). Previously, we could demonstrate that Fas ligand (FasL/CD95L)-expressing 'killer-antigen-presenting cells' can be generated from human monocyte-derived mature DC (mDC) using adenoviral gene transfer. To evaluate whether these FasL-expressing mDC (mDC-FasL) could eliminate alloreactive primary human T cells in vitro, co-culture experiments were performed. Proliferation of human T cells was markedly reduced in primary co-cultures with allogeneic mDC-FasL, whereas a strong proliferative T-cell response could be observed in co-cultures with enhanced green fluorescent protein-transduced mDC. Inhibition of T-cell proliferation was related to the transduction efficiency, and the numbers of mDC-FasL present in co-cultures. In addition, proliferation of pre-activated alloreactive CD4+ and CD8+ T cells could be almost completely inhibited in secondary co-cultures using mDC-FasL as stimulatory cells, which was the result of induction of apoptosis in the majority of preactivated T cells. The specific deletion of alloreactive T cells by mDC-FasL was confirmed by an unaffected proliferative response of surviving T cells towards allogeneic 'third-party' peripheral blood mononuclear cells in a third stimulation, or upon unspecific stimulation with anti-CD3/CD28 beads. The results of this study demonstrate that allospecifically activated T cells are efficiently eliminated by mDC-FasL, supporting further investigations to apply FasL-expressing 'killer-DC' as a novel strategy for the treatment of allograft rejection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ANTIGEN-PRESENTING CELLS; IN-VIVO; IMMUNE-RESPONSE; TOLERANCE; INDUCTION; CD95; APOPTOSIS; SYSTEM; DEATH; TOOL; dendritic cells; graft-versus-host disease; T cell; tolerance |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jun 2020 08:16 |
| Last Modified: | 22 Jun 2020 08:16 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20923 |
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