Figure 1

CD95L-expressing APC down-modulate T cell responses. High density CD95L, as expressed on transfectants or certain activated APC or mimicked by high amounts of CD95 agonists in vitro, engages membrane CD95 and interferes with proximal TCR signaling by inhibiting the phosphorylation of ZAP-70, PLCγ and PKC, leading to inefficient nuclear translocation of transcription factors like NFAT, NF-κB and AP-1 (Jun/c-Fos). CD95 engagement under such conditions also prevents activation of caspases and MAPK as well as Ca²⁺-mobilization. Subsequently, TCR-induced cytokine production and upregulation of activation markers are impaired, resulting in a CD95L-mediated complete block of cell cycle progression in naïve T cells.