IL-4 is a mediator of IL-12p70 induction by human Th2 cells: Reversal of polarized Th2 phenotype by dendritic cells

IL-12 is a key inducer of Th1-associated inflammatory responses, protective against intracellular infections and cancer, but also involved in autoimmu ne tissue destruction. We report that human Th2 cells interacting with mono cyte-derived dendritic cells (DC) effectively induce bioactive IL-12p70 and revert to Th0/Th1 phenotype. In contrast, the interaction with B cells pre serves polarized Th2 phenotype. The induction of IL-12p70 in Th2 cell-DC co cultures is prevented by IL-4-neutralizing mAb, indicating that IL-4 acts a s a Th2 cell-specific cofactor of IL-12p70 induction. Like IFN-gamma, IL-4 strongly enhances the production of bioactive IL-12p70 heterodimer in CD40 ligand-stimulated DC and macrophages and synergizes with IFN-gamma at low c oncentrations of both cytokines, However, in contrast to IFN-gamma, IL-4 in hibits the CD40 ligand-induced production of inactive IL-12p40 and the prod uction of either form of IL-12 induced by LPS, which may explain the view o f IL-4 as an IL-12 inhibitor. The presently described ability of IL-4 to ac t as a cofactor of Th cell-mediated IL-12p70 induction may allow Th2 cells to support cell-mediated immunity in chronic inflammatory states, including cancer, autoimmunity, and atopic dermatitis.