Prostaglandin E-2 and IL-4 provide naive CD4(+) T cells with distinct inhibitory signals for the priming of IFN-gamma production

We investigated the effects of prostaglandin Ep and IL-4 on the acquisition of cytokine-producing ability by naive CD4(+) T cells in human umbilical cord blood, The presence of PGE(2) or IL-4 at primary stimulation inhibited the production of IFN-gamma 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 PGE(2)-treated cells but not in IL-4-treated or control cells. The signal provided by PGE(2), 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 PGE(2)- and IL-4-treated cells were not different. Our results suggest that both PGE(2) and IL-4 play important roles with distinct mechanisms in inhibiting the priming of IFN-gamma production of naive CD4(+) T cells. (C) 1997 Academic Press.