SIGNALING PATHWAYS CAN INCREASE FAS EXPRESSION IN HUMAN THYMOCYTES

Fas, a cell surface receptor, can induce apoptosis after cross-linking with its ligand, Fewer than 3% of human thymocytes strongly express F as. We report that Fas antigen expression can be upregulated by two si gnaling pathways in vitro, one mediated by anti-CDB and the other by i nterleukin-7 + interferon-gamma. The two signaling pathways differed i n several respects. (1) Fas expression increased in all thymic subsets after cytokine activation, but only in the CD4 lineage after anti-CDB activation. (2) Fas upregulation was inhibited by cyclosporin A (a ca lcineurin inhibitor) in anti-CD3-activated but not in cytokine-activat ed thymocytes, (3) Cycloheximide (a metabolic inhibitor) inhibited Fas upregulation in cytokine-activated thymocytes but not in anti-CD3-act ivated thymocytes, (4) Cytokine-activated thymocytes were more suscept ible than anti-CD3-activated thymocytes to Fas-induced apoptosis, a di fference mainly accounted for by CD4(+) cells. The nature of the stimu lus might thus influence the susceptibility of human thymocytes to Fas -induced apoptosis. (C) 1998 by The American Society of Hematology.