Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction

Dendritic cells (DC) are key initiators of primary immune responses, Myeloi d DC can secrete IL-12, a potent Th1-driving factor, and are often viewed a s Th1-prompting APC, Here we show that neither a Th1- nor a Th2-inducing fu nction is an intrinsic attribute of human myeloid DC, but both depend on en vironmental instruction, Uncommitted immature DC require exposure to IFN-ga mma, at the moment of induction of their maturation or shortly thereafter, to develop the capacity to produce high levels of IL-12p70 upon subsequent contact with naive Th cells. This effect is specific for IFN-gamma and is n ot shared by other IL-12-inducing factors. Type 1-polarized effector DC, ma tured in the presence of IFN-gamma, induce Th1 responses, in contrast to ty pe 2-polarized DC matured in the presence of PGE(2) that induce Th2 respons es. Type 1-polarized effector DC are resistant to further modulation, which may facilitate their potential use in immunotherapy.