Two 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 Fas. We report that Fas antigen expression can be upregulated by two signaling pathways in vitro, one mediated by anti-CD3 and the other by interleukin-7 + interferon-gamma. The two signaling pathways differed in several respects. (1) Fas expression increased in all thymic subsets after cytokine activation, but only in the CD4 lineage after anti-CD3 activation. (2) Fas upregulation was inhibited by cyclosporin A (a calcineurin inhibitor) in anti-CD3-activated but not in cytokine-activated thymocytes. (3) Cycloheximide (a metabolic inhibitor) inhibited Fas upregulation in cytokine-activated thymocytes but not in anti-CD3-activated thymocytes. (4) Cytokine-activated thymocytes were more susceptible than anti-CD3-activated thymocytes to Fas-induced apoptosis, a difference mainly accounted for by CD4(+) cells. The nature of the stimulus might thus influence the susceptibility of human thymocytes to Fas-induced apoptosis.