Distinct dendritic cell subsets differentially regulate the class of immune response in vivo

Dendritic cells (DCs) are unique in their ability to stimulate T cells and initiate adaptive immunity. Injection of mice with the cytokine FIt3-ligand (FL) dramatically expands mature lymphoid and myeloid-related DC subsets. In contrast, injection of a polyethylene glycol-modified form of granulocyt e/macrophage colony-stimulating factor (GM-CSF) into mice only expands the myeloid-related DC subset. These DC subsets differ in the cytokine profiles they induce in T cells in vivo. The lymphoid-related subset induces high l evels of the Th1 cytokines interferon gamma and interleukin (IL)-2 but litt le or no Th2 cytokines. In contrast, the myeloid-related subset induces lar ge amounts of the Th2 cytokines IL-4 and IL-IO, in addition to interferon g amma and IL-2. FL or GM-CSF-treated mice injected with soluble ovalbumin di splay dramatic increases in antigen-specific antibody titers, but the isoty pe profiles seem critically dependent on the cytokine used. Although FL tre atment induces up to a 10,000-fold increase in ovalbumin-specific IgG2a and a more modest increase in IgG1 titers, GM-CSF treatment favors a predomina ntly IgG1 response with little increase in IgG2a levels. These data suggest that distinct DC subsets have strikingly different influences on the type of immune response generated in vivo and may thus be targets for pharmacolo gical intervention.