Blood, Vol. 92 No. 4 (August 15), 1998:
pp. 1297-1307
Two Signaling Pathways Can Increase Fas Expression in Human
Thymocytes
Nathalie Moulian,
Jocelyne Bidault,
Claude Planché, and
Sonia Berrih-Aknin
From CNRS UPRESA, Hôpital Marie-Lannelongue, Le Plessis
Robinson, France.
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-
. 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.
© 1998 by The American Society of Hematology.
