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.
CNRS UPRESA, Hôpital Marie-Lannelongue, Le Plessis Robinson, France.
N
N
Moulian
J
J
Bidault
C
C
Planché
S
S
Berrih-Aknin
D017209:Apoptosis / Q000187:drug effects*; D017252:CD3 Complex / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D065095:Calcineurin Inhibitors; D017637:Clonal Deletion / Q000502:physiology; D003513:Cycloheximide / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000494:pharmacology*; D015851:Interleukin-7 / Q000494:pharmacology*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology*; D015854:Up-Regulation / Q000187:drug effects*; D019014:fas Receptor / Q000096:biosynthesis* / Q000235:genetics
D017252:CD3 Complex; D065095:Calcineurin Inhibitors; D004791:Enzyme Inhibitors; D015851:Interleukin-7; D011500:Protein Synthesis Inhibitors; D019014:fas Receptor; D007371:Interferon-gamma; D016572:Cyclosporine; D003513:Cycloheximide