DIFFERENTIAL REGULATION BY PHORBOL-MYRISTATE ACETATE OF IFN-GAMMA AND IL-4 EXPRESSION IN ANTI-CD3 STIMULATED MOUSE SPLEEN-CELLS

Expression of messenger RNA (mRNA) specific for two cytokines representative of both Th1 and Th2 cell subtypes, interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) respectively, was analysed in murine spleen cells stimulated in vitro with an anti-CD3 monoclonal antibody (mAb). This stimulation induced predominantly an IFN-gamma message. In contrast, in the presence of phorbol myristate acetate (PMA), the expression of IFN-gamma was decreased whereas the IL-4 message was dramatically enhanced. These results were confirmed by Polymerase Chain Reaction (PCR) analysis and extended to include another T-cell activator [Concanavalin A (Con A)]. The results suggest the existence of a differential pathway of activation for the Th subpopulations or a differential regulation of the T helper lymphokine gene expression by PMA-induced signals.