Blood, Vol. 93 No. 8 (April 15), 1999:
pp. 2660-2670
Functional Fas Expression in Human Thymic Epithelial Cells
Nathalie Moulian,
Claire Renvoizé,
Colette Desodt,
Alain Serraf, and
Sonia Berrih-Aknin
From CNRS UPRESA, Hôpital Marie-Lannelongue, Le Plessis
Robinson, France; and INSERM U461, Faculté de Pharmacie,
Chatenay-Malabry, France (CNRS UPRESA and U461 are affiliated to the
Institut Paris-Sud sur les Cytokines).
Fas, a cell surface receptor, can induce apoptosis after
cross-linking with its ligand. We report that Fas antigen is
constitutively expressed in medullary epithelial cells of the human
thymus. Expression is decreased in cultured thymic epithelial cells
(TEC), similarly to HLA-DR antigen. TEC are resistant to
anti-Fas-induced apoptosis after 4 days of primary culture, and this
resistance is reversed by concomitant addition of cycloheximide.
Cycloheximide also downregulated the expression of Fas-associated
phosphatase-1, which has been found to inhibit Fas-induced apoptosis.
This phosphatase could be involved in the resistance to Fas-induced
apoptosis observed on day 4 of TEC culture. When TEC were subcultured
after 10 to 13 days of primary culture, exposure to interleukin-1-
,
tumor necrosis factor-
, and interferon-
, alone or together,
reinduced Fas mRNA and protein expression. In coculture with activated
thymocytes, TEC also upregulated Fas protein expression.
Cytokine-activated TEC became sensitive to apoptosis induced by an
agonistic anti-Fas antibody. This apoptosis was inhibited by Z-VAD-fmk
but not by Z-DEVD-fmk and DEVDase activity was slightly increased in
Fas-stimulated TEC, suggesting that DEVDase activity is not sufficient
to induce TEC apoptosis. Taken together, these data show that the Fas
receptor is expressed in medullary epithelial cells of the human thymus and is able to induce apoptosis.
