Abstract
The objective of the present study was to evaluate the aptitude of TRAIL gene expression for inducing apoptosis in co-cultivated T-cells. This should allow preparing a strategy for the development of a durable, allogenic skin substitute based on the induction of an immune-privileged transplant. In order to counteract the significant potential of rejection in transplanted allogenic keratinocytes, we created a murine keratinocyte cell line which expressed TRAIL through stable gene transfer. The exogenic protein was localized on the cellular surface and was not found in soluble condition as sTRAIL. Contact to TRAIL expressing cells in co-culture induced cell death in sensitive Jurkat-cells, which was further intensified by lymphocyte activation. This cytotoxic effect is due to the induction of apoptosis. We therefore assume that the de-novo expression of TRAIL in keratinocytes can trigger apoptosis in activated lymphocytes and thus prevent the rejection of keratinocytes in allogenic, immune-privileged transplants.
Highlights
Members of the TNF ligand family control and conduct numerous immunological and inflammation-related reactions
Generating a keratinocyte cell-line to express TNF-related apoptosis-inducing ligand (TRAIL) The present study investigated the capacity of overexpressed TRAIL to induce apoptosis in co-cultivated T-cells
Membrane fluorescence is characteristic for apoptosis. c Phase-contrast-imaging of a Jurkat cell after 48 hours of co-culture with JB6-pcDNA5/ FRT CAT. d Annexin V/Propidiumiodide dyed Jurkat cell after 48 hours of co-culture with JB6-pcDNA5/FRT CAT
Summary
Members of the TNF ligand family control and conduct numerous immunological and inflammation-related reactions. The Fas-FasL system and its associated mechanism of activation-induced cell death play an important role for the maintenance of hemostasis of the lymphoid system and the induction of immune tolerance [1]. The TNF-related apoptosis-inducing ligand (TRAIL) was identified as a homologue of the Fas-ligand (FasL) [2]. Five different receptors for TRAIL have been described and all belong to the TNF receptor family. The soluble receptor osteoprotegerin (OPG) belongs to a different sub-family and binds the ligand RANKL/OPGL as well. Following ligand binding and activation of cytoplasmatic death domains, TRAIL-R1 and TRAIL-R2 start series (page number not for citation purposes)
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