Reimers Kerstin, Radtke Christine, Choi Claudia Y, Allmeling Christina, Kall Susanne, Kiefer Paul, Muehlberger Thomas, Vogt Peter M
Department of Plastic, Hand and Reconstructive Surgery, Medical School Hannover Podbielskistraße 380, 30659 Hannover, Germany.
University Duesseldorf, Moorenstrasse 5, 40225 Duesseldorf, Germany.
Ann Surg Innov Res. 2009 Nov 19;3:13. doi: 10.1186/1750-1164-3-13.
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.
本研究的目的是评估TRAIL基因表达诱导共培养T细胞凋亡的能力。这将有助于制定一种策略，以开发基于诱导免疫特权移植的持久同种异体皮肤替代物。为了对抗移植的同种异体角质形成细胞中显著的排斥潜力，我们创建了一种通过稳定基因转移表达TRAIL的小鼠角质形成细胞系。外源性蛋白定位于细胞表面，未发现以可溶性sTRAIL形式存在。共培养中与表达TRAIL的细胞接触会诱导敏感的Jurkat细胞死亡，淋巴细胞激活会进一步加剧这种死亡。这种细胞毒性作用是由于凋亡的诱导。因此，我们认为角质形成细胞中TRAIL的从头表达可触发活化淋巴细胞的凋亡，从而防止同种异体免疫特权移植中角质形成细胞的排斥。
