Fas ligand (FasL) is a death factor that binds to its receptor, Fas, atzd induces apoptosis. Two mutations that accelerate autoimmune disease, Ipr and gld, are known to correspond to mutations within genes encoding Fas and FasL, respectively. Here, Shigekazu Nagata and Takashi Suda summarize current knowledge of Fas and FasL, and discuss the physiological role of the Fas system in T-cell development, cytotoxicity and cytotoxic T lymphocyte (CTL)-mediated autoimmune disease.

Monoclonal antibodies (mAbs) raised against the Fas (APO-l) cell-surface protein have cell-killing activity’,‘. Molecular cloning of Fas cDNA has shown that Fas is a type I membrane protein belonging to the tumor necrosis factor (TNF)/nerve growth factor (NGF) receptor family-3 6. Mouse cell lines expressing human Fas have been established, and crosslinking with antibody against human Fas induces apoptosis of these cells. From these results, it was concluded that Fas transduces an apoptotic signal into cells, and that anti-Fas antibody works as an agonist for the Fas protein. Northern blot hybridization of mouse tissues have indicated that Fas mRNA is abundantly expressed in the thymus, liver, heart, lung, kidney and ovaryj, but is weakly expressed in various other tissues (T. Suda and S. Nagata, unpublished).