PROSTAGLANDIN E-2 AND IL-4 PROVIDE NAIVE CD4(-CELLS WITH DISTINCT INHIBITORY SIGNALS FOR THE PRIMING OF IFN-GAMMA PRODUCTION() T)

We investigated the effects of prostaglandin Ep and IL-4 on the acquis ition of cytokine-producing ability by naive CD4(+) T cells in human u mbilical cord blood, The presence of PGE(2) or IL-4 at primary stimula tion inhibited the production of IFN-gamma at secondary stimulation, a nd the combination of these stimuli resulted in cooperative effects. D uring primary stimulation with anti-CD3, the intracellular cAMP level was elevated in PGE(2)-treated cells but not in IL-4-treated or contro l cells. The signal provided by PGE(2), but not by IL-4, was inhibited with RpcAMP, indicating that it was mediated by cAMP. After different iation into Th2-like cells, cAMP levels in PGE(2)- and IL-4-treated ce lls were not different. Our results suggest that both PGE(2) and IL-4 play important roles with distinct mechanisms in inhibiting the primin g of IFN-gamma production of naive CD4(+) T cells. (C) 1997 Academic P ress.