Paulsen Maren, Mathew Biny, Qian Jing, Lettau Marcus, Kabelitz Dieter, Janssen Ottmar
Institute of Immunology, University Hospital Schleswig-Holstein Campus Kiel, Arnold-Heller-Strasse 3, Building 17, D-24105 Kiel, Germany.
Int Immunol. 2009 May;21(5):587-98. doi: 10.1093/intimm/dxp028. Epub 2009 Mar 30.
Activation of resting T cells in vitro is triggered by combined TCR and CD28 engagement and can be modulated by simultaneous ligation of various other surface receptors. Although the Fas ligand (FasL) is best known for its capacity to initiate cell death in Fas-bearing cells, it has recently been implicated in the regulation of T cell activation. Thus, a cross-talk between the TCR and FasL is likely, but far from being biochemically elucidated. We now report that FasL engagement by immobilized but not soluble FasFc fusion protein and anti-FasL polyclonal antibody blocks the activation of human peripheral T cells even in the presence of CD28 co-stimulation. The data presented here stress the importance of the Fas/FasL system for signal initiation via the TCR-CD3 complex and provide further arguments for a retrograde signaling capacity of FasL or a crucial role of Fas as a co-stimulatory molecule.
体外静息T细胞的激活是由TCR和CD28的联合作用触发的，并且可以通过同时连接各种其他表面受体来调节。尽管Fas配体（FasL）最出名的是其在携带Fas的细胞中引发细胞死亡的能力，但最近它被认为参与了T细胞激活的调节。因此，TCR和FasL之间可能存在相互作用，但远未在生化方面得到阐明。我们现在报告，固定化的但不是可溶性的FasFc融合蛋白和抗FasL多克隆抗体与FasL的结合即使在存在CD28共刺激的情况下也能阻断人外周血T细胞的激活。这里给出的数据强调了Fas/FasL系统对于通过TCR-CD3复合物启动信号的重要性，并为FasL的逆行信号传导能力或Fas作为共刺激分子的关键作用提供了进一步的论据。
