Phorbol ester-inactivation of cloned cytotoxic T lymphocytes: restoration of lytic activity by interleukin 2 and induction of interferon production are separable events

Abstract

We have examined the interrelationship between Interleukin 2 (IL 2) and Interferon gamma (IFN gamma) for the induction of cytolytic activity from inactivated cloned cytotoxic T lymphocytes (CTL). In previous work we showed that treatment of cloned CTL with phorbol myristate acetate (PMA) inactivated their cytolytic function and that these inactivated cells provided an experimental approach to define the cytokines necessary for the induction of cytolysis. We further showed that IL 2 could provide a sufficient signal to restore cytolytic activity to inactivated cells by a process that was independent of cellular proliferation. Here we report that reactivation of the lytic response by IL 2 did not correlate with IFN production. IL 2 had the ability to restore lytic activity to PMA-treated cells but did not induce IFN gamma production. Similarly, IL 2 augmented the preexisting lytic response of non-PMA-treated cloned cells without stimulating IFN gamma production. However, PMA-treated and untreated cells had the capacity to produce IFN gamma when cultured with mitogen. These results suggest that IL 2 mediated reactivation of the cytolytic response and IFN gamma production by a cloned CTL appear to be regulated independently.