Cytokines Regulate the Capacity of CD8α+ and CD8α− Dendritic Cells to Prime Th1/Th2 Cells In Vivo

Prior studies have shown that subclasses of dendritic cells (DC) direct the development of distinct Th populations in rodents and in humans. In the mouse, we have recently shown that administration of Ag-pulsed CD8α− DC induces a Th2-type response, whereas injection of CD8α+ DC leads to Th1 differentiation. To define the DC-derived factors involved in the polarization of Th responses, we injected either subset purified from mice genetically deficient for IFN-γ, IL-4, IL-12, or IL-10 into wild-type animals. In this work, we report that DC-derived IL-12 and IFN-γ are required for Th1 priming by CD8α+ DC, whereas IL-10 is required for optimal development of Th2 cells by CD8α− DC. The level of IL-12 produced by the DC appears to determine the Th1/Th2 balance in vivo. We further show that the function of DC subsets displays some flexibility. Treatment of DC with IL-10 in vitro induces a selective decrease in the viability of CD8α+ DC. Conversely, incubation with IFN-γ down-regulates the Th2-promoting capacities of CD8α− DC and increases the Th1-skewing properties of both subsets.