It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (T(H)1) or T(H)2 cells. Human monocyte (pDC1)-derived dendritic cells (DC1) were found to induce T(H)1 differentiation, whereas dendritic cells (DC2) derived from CD4(+)CD3(-)CD11c(-) plasmacytoid cells (pDC2) induced T(H)2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The T(H)2 cytokine IL-4 enhanced DC1 maturation and killed pDC2, an effect potentiated by IL-10 but blocked by CD40 Ligand and interferon-gamma, Thus, a negative feedback Loop from the mature T helper cells may selectively inhibit prolonged T(H)1 or T(H)2 responses by regulating survival of the appropriate dendritic cell subset.