Abstract

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-γ. 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.