Prostaglandin E2and IL-4 Provide Naive CD4+T Cells with Distinct Inhibitory Signals for the Priming of IFN-γ Production

We investigated the effects of prostaglandin E2and IL-4 on the acquisition of cytokine-producing ability by naive CD4+T cells in human umbilical cord blood. The presence of PGE2or IL-4 at primary stimulation inhibited the production of IFN-γ at secondary stimulation, and the combination of these stimuli resulted in cooperative effects. During primary stimulation with anti-CD3, the intracellular cAMP level was elevated in PGE2-treated cells but not in IL-4-treated or control cells. The signal provided by PGE2, but not by IL-4, was inhibited with RpcAMP, indicating that it was mediated by cAMP. After differentiation into Th2-like cells, cAMP levels in PGE2- and IL-4-treated cells were not different. Our results suggest that both PGE2and IL-4 play important roles with distinct mechanisms in inhibiting the priming of IFN-γ production of naive CD4+T cells.