CD95/Fas-triggered apoptosis of activated T lymphocytes is prevented by dendritic cells through a CD58-dependent mechanism

T-cell apoptosis is a mechanism regulating T-cell homeostasis. Activation r enders T cells susceptible to activation-induced cell death, a process medi ated through CD95 ligand/CD95 (Apo-1/Fas) ligation, The aim of this study w as to test whether antigen-presenting cells can inhibit CD95/Fas-triggered activation-induced cell death. Dendritic cells (DC), which are highly effec tive antigen-presenting cells, mere generated in vitro from human periphera l blood monocytes by culture in granulocyte-macrophage colony-stimulating f actor and interleukin 4, Subsequently, DC were cocultured with activated T cells and the effect of DC on CD95/Fas-mediated apoptosis was determined. C oculture with increasing amounts of DC prevented CD95/Fas-triggered apoptos is in a dose-dependent fashion by inhibiting activation of caspase 8 and ca spase 3, This protective effect of the DC on T-cell death could be blocked by 50% by adding an anti-CD58 antibody, whereas further addition of anti-CD 80 (B7.1) and anti-CD86 (B7.2) led to an even more pronounced effect. Our f indings suggest that DC can protect T cells from activation-induced cell de ath, with CD58 ligation playing a key role. (C) 1999 International Society for Experimental Hematology. Published by Elsevier Science Inc.