Suppressive activity of 12-O-tetradecanoyl phorbol-13-acetate on the induction of cytotoxic T cells in vitro.

The effect of phorbol esters on the induction of cytotoxic T cells was studied in vitro. 12-O-Tetradecanoyl phorbol-13-acetate (TPA) suppressed the induction of hapten-reactive cytotoxic T cells when added to the in vitro culture. Other phorbol derivatives such as phorbol, phorbol-13-monoacetate and phorbol-12-monomyristate had no suppressive activity. The suppressive activity of TPA was not due to either a cytotoxic effect or a change of the kinetics of the cytotoxic T cell development. The suppressive activity was evident when TPA was added at the early stage of the induction culture of cytotoxic T cells, but not at the later stage. Furthermore, TPA did not suppress the effector phase of cytotoxic T cell action on the target cells. A brief treatment of spleen cells with TPA induced suppressor T cell activity. This suppressive activity of TPA was correlated with the stimulation activity of lymphocytes. Thus, TPA stimulates the proliferative T cell response on the one hand and suppresses the induction of cytotoxic T cells on the other. The mechanism of the suppression of induction of cytotoxic T cells by TPA and the role of tumor promoters in carcinogenesis are discussed.