NATURAL HUMAN INTERFERON-ALPHA AUGMENTS APOPTOSIS IN ACTIVATED T-CELLLINE

We have previously shown that interferon-alpha (IFN-alpha) augments in terleukin-2 (IL-2) production in mitogen-activated but not unstimulate d T cells (1). Here, we studied the effect of IFN-alpha on activation- driven cell death (apoptosis) using a human leukemia T cell line, MOLT -16, as a T cell activation model. IFN-alpha alone had no effect on ei ther the IL-2 production or apoptosis of MOLT-16 cells, but significan tly increased both the IL-2 production and apoptosis in the MOLT-16 ce lls after phytohemagglutinin (PHA) stimulation as determined by CTLL-2 assay and by flow cytometric analysis using propidium iodide (PI) sta ining. Since IL-2 has been shown to induce apoptosis in some systems, we next evaluated whether the apoptosis in MOLT-16 cells was due to en dogenous IL-2 production upon PHA stimulation. However, the addition o f exogenous IL-2 to unstimulated cultures of MOLT-16 did not induce DN A fragmentation, a characteristic feature of apoptosis, as determined by DNA electrophoresis and by flow cytometric analysis with PI-stained cells. Furthermore, anti-IL-2 antibody did not prevent PHA-induced DN A fragmentation in MOLT-16 cells. Thus, we conclude that both PHA-indu ced IL-2 production and apoptosis are outcomes of T cell activation an d that IFN-alpha may exert immunoregulatory effects on T cell activati on by augmenting both processes. (C) 1994 Academic Press, Inc.