Induction of Fas Ligand-Mediated Apoptosis by Interferon-α

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