PROSTAGLANDIN E(2) AT PRIMING OF NAIVE CD4(-CELLS INHIBITS ACQUISITION OF ABILITY TO PRODUCE IFN-GAMMA AND IL-2, BUT NOT IL-4 AND IL-5() T)

We investigated the effect of prostaglandin E(2) on the acquisition of cytokine-producing ability by naive CD4(+) T cells in human cord bloo d. Naive CD4(+) T cells were stimulated for 3 days with mouse monoclon al anti-CD3 Ab, then washed and expanded in IL-2-containing medium for 3 more days. These activated T cells produced IL-2, IL-4, IL-5, and I FN-gamma upon stimulation with PMA and ionomycin. PGE(2) added at prim ing of naive T cells inhibited the production of IL-2 and IFN-gamma, b ut not of IL-4 and IL-5, in a dose-dependent manner. This change in th e cytokine production profile induced by PGE(2) was maintained in T ce lls restimulated with anti-CD3 in the absence of PGE(2), expanded by I L-2, and stimulated with PMA and ionomycin. The mRNA expression of IFN -gamma and IL-2, but not that of IL-4, was also decreased in these cel ls. Forskolin and dibutyryl cAMP had a similar effect. PGE(2) must exi st at an early stage of T cell activation to inhibit priming for IL-2 and IFN-gamma production. PGE(2) also showed this effect, even in the presence of exogenous IFN-gamma, at the primary stimulation. These res ults indicate that PGE(2) inhibits the acquisition of the ability to p roduce IL-2 and IFN-gamma by acting directly on naive T cells. Our res ults suggest that PGE(2) plays a role in facilitating the development of the Th2-type cytokine production profile.