Induction of Fas ligand-mediated apoptosis by interferon-alpha

Interferon-alpha (IFN-alpha) was among the first cytokines studied and the earliest to be used in clinical medicine for the treatment of viral infecti ons and malignancies. Although the capacity of IFN-alpha to augment NK cell cytotoxicity against virus-infected target cells or tumor cells is well es tablished, the mechanism has not been fully elucidated. Here we report that IFN-alpha stimulation of PBMC from healthy donors induces Fas (CD95) ligan d (FasL) transcription and leads to increased cell surface Fast expression exclusively on the NK cell fraction. Furthermore, IFN-alpha augments the Fa st-mediated cytotoxicity of normal PBMC against Fas-sensitive lymphoid tumo r cells. In the context of innate immunity, induction of Fast by IFN-alpha can be viewed as an efficient mechanism to potentiate NR cell cytotoxicity in the presence of harmful targets, such as virally infected or transformed cells. (C) 2000 Academic Press.