PGE2 inhibits IL-2 and IL-4-dependent proliferation of CTLL-2 and HT2 cells

The cytotoxic T cell line CTLL-2 and the T helper cell line HT2 proliferate in response to interleukin 2 (IL-2) or IL-4 without requiring stimulation by antigen through the T cell receptor and therefore lend themselves for studies of IL-2- and IL-4-dependent proliferation and signalling through their cognate receptors. Here we have used CTLL-2 and HT2 cells to investigate the effect of the inflammatory mediator prostaglandin E2 (PGE2) on IL-2- and IL-4-dependent proliferation. PGE2 inhibited IL-2- as well as IL-4-dependent proliferation of both CTLL-2 and HT2 cells, with IL-4-dependent proliferation being more sensitive than IL-2-dependent proliferation and CTLL-2 cells being more sensitive than HT2 cells. A quantitative dose-effect analysis revealed a two-step increase of inhibition (around 10(-10) M and 10(-5) M PGE2) for all combinations of cells and cytokines approaching 100% at high concentrations of PGE2. The data suggest that even in cases where synthesis of IL-2 and IL-4 is differentially affected by PGE2, IL-2- and IL-4-dependent T cells may still be similarly sensitive to PGE2 by way of their cytokine responsiveness. Furthermore, the effects of PGE2 may be mediated by more than one functional binding site or receptor subtype. PGE2 levels are an important consideration when CTLL-2 and HT2 cells are used for the measurement of IL-4 and IL-2.