Thiols prevent Fas (CD95)‐mediated T cell apoptosis by down‐regulating membrane Fas expression

Thiol antioxidants have been shown to protect cells against apoptosis. Based on the role of Fas in T cell apoptosis, we investigated the effect of thiols on Fas expression. We report that the thiol N‐acetyl‐L‐cysteine (NAC) prevents the induction of Fas on human peripheral blood T cells in a dose‐dependent manner. It also down‐regulates in a time‐ and dose‐dependent manner Fas expression on Fas‐expressing T cells. Although these effects were not mediated through de novo glutathione synthesis, only compounds with a free thiol group decreased membrane Fas expression. The decrease of Fas expression induced by NAC was not associated with a modulation of Fas mRNA transcription nor with an inter‐nalization, suggesting that NAC may affect the processing of Fas. Indeed, a soluble immunoreactive form of Fas was detected by ELISA and by Western blotting in the supernatants of Fas‐expressing T cells treated with NAC. As a functional consequence, NAC partly protected Jurkat cells against Fas‐mediated apoptotic cell death. Thus, this study shows that, by regulating Fas expression, the cytoprotective properties of NAC can be extended to Fas‐mediated cell death.