Functional Fas expression in human thymic epithelial cells

Fas, a cell surface receptor, can induce apoptosis after cross-linking with its ligand. We report that Fas antigen is constitutively expressed in medu llary epithelial cells of the human thymus. Expression is decreased in cult ured thymic epithelial cells (TEG), similarly to HLA-DR antigen. TEC are re sistant to anti-fas-induced apoptosis after 4 days of primary culture, and this resistance is reversed by concomitant addition of cycloheximide. Cyclo heximide also downregulated the expression of Fas-associated phosphatase-1, which has been found to inhibit Fas-induced apoptosis. This phosphatase co uld be involved in the resistance to pas-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-beta, tumor necrosis factor-alpha, and i nterferon-gamma, alone or together, reinduced Fas mRNA and protein expressi on. In coculture with activated thymocytes, TEC also upregulated Fas protei n expression. Cytokine-activated TEC became sensitive to apoptosis induced by an agonistic anti-Fas antibody. This apoptosis was inhibited by Z-VAD-fm k but not by Z-DEVD-fmk and DEVDase activity was slightly increased in Fas- stimulated TEC, suggesting that DEVDase activity is not sufficient to induc e TEC apoptosis. Taken together these data show that the Fas receptor is ex pressed in medullary epithelial cells of the human thymus and is able;to in duce apoptosis. (C) 1999 by The American Society of Hematology.