IL-12-DEFICIENT DENDRITIC CELLS, GENERATED IN THE PRESENCE OF PROSTAGLANDIN E-2, PROMOTE TYPE-2 CYTOKINE PRODUCTION IN MATURING HUMAN NAIVET-HELPER CELLS

We studied to what extent the presence of an inflammatory mediator PGE (2), during the development of dendritic cells (DC) affects their subs equent ability to induce Th1- and Th2-type cytokines in maturing naive Th cells, PGE(2) (10(-9)-10(-6) M) did not alter the morphology or th e expression of class II MHC and costimulatory molecules on DC obtaine d from monocytes in the presence of granulocyte-macrophage CSF and IL- 4, although at concentrations above 10(-8) MI PGE(2) prevented the acq uisition of CD1a marker, Both control DC and DC maturing in the presen ce of PGE(2) (PGE(2)-DC) were potent stimulators of naive Th cells, In contrast to control DC, which produced high amounts of IL-12 and trac e amounts of IL-10, PGE(2)-DC produced no IL-12 and high amounts of IL -10 when stimulated in the absence of PGE(2), This distinct cytokine p rofile of PGE(2)-DC was stable for at least 48 h of additional culture in the absence of PGE(2), Control DC induced the development of Th0-l ike cells from superantigen-activated naive Th cells, whereas PGE(2)-D C promoted the development of Th cells that produced high amounts of I L-4 and IL-5, Experiments using IL-12-neutralizing Abs or rlL-12 indic ated a crucial role of IL-12 deficiency in the induction of type 2 cyt okine profiles, These findings suggest that elevated levels of PGE(2) promote type 2 Th responses by stably impairing the ability of maturin g DC to produce IL-12, Since type 2 Th responses are protective in sev eral Th1-related autoimmune disorders, PGE(2)-DC may be considered for use in immunotherapy.