Perforin-Independent CD8+ T-Cell–Mediated Cytotoxicity of Alveolar Epithelial Cells Is Preferentially Mediated by Tumor Necrosis Factor- α

CD8+ T cells appear to play an important pathophysiologic role in many inflammatory lung diseases. The primary effector function of this T-cell subset is cytolysis of virus-infected cells, and it is widely believed that there are two primary molecular mechanisms by which this occurs: the perforin/granzyme-mediated pathway of cytolysis, and the Fas ligand (FasL)–Fas (CD95/APO-1) pathway of induction of target-cell apoptosis. This conclusion is based primarily on data obtained with hematopoetic cell lines as target cells. There is also a growing body of evidence that Fas is involved in the transduction of apoptotic signals in a variety of inflammatory disease states, particularly involving the liver and the lung. In the study reported here we took advantage of a novel in vitro assay to directly assess the effector mechanisms employed in CD8+ T-cell–mediated cytolysis of alveolar epithelial cells. We present evidence that FasL-induced, Fas-mediated apoptosis does not directly contribute to T-cell–mediated cy...