Reciprocal control of T helper cell and dendritic cell differentiation

Science. 1999 Feb 19;283(5405):1183-6. doi: 10.1126/science.283.5405.1183.

Abstract

It is not known whether subsets of dendritic cells provide different cytokine microenvironments that determine the differentiation of either type-1 T helper (TH1) or TH2 cells. Human monocyte (pDC1)-derived dendritic cells (DC1) were found to induce TH1 differentiation, whereas dendritic cells (DC2) derived from CD4+CD3-CD11c- plasmacytoid cells (pDC2) induced TH2 differentiation by use of a mechanism unaffected by interleukin-4 (IL-4) or IL-12. The TH2 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 TH1 or TH2 responses by regulating survival of the appropriate dendritic cell subset.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • CD40 Antigens
  • CD40 Ligand
  • Cell Differentiation
  • Cell Lineage
  • Cell Survival
  • Cells, Cultured
  • Coculture Techniques
  • Dendritic Cells / cytology*
  • Dendritic Cells / immunology
  • Feedback
  • Humans
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / pharmacology
  • Interleukin-12 / biosynthesis
  • Interleukin-12 / pharmacology
  • Interleukin-12 / physiology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / pharmacology
  • Interleukin-4 / physiology*
  • Interleukins / biosynthesis
  • Interleukins / pharmacology
  • Lymphocyte Activation
  • Membrane Glycoproteins / pharmacology
  • Stem Cells / cytology
  • Th1 Cells / cytology*
  • Th1 Cells / immunology
  • Th2 Cells / cytology*
  • Th2 Cells / immunology

Substances

  • CD40 Antigens
  • Interleukins
  • Membrane Glycoproteins
  • CD40 Ligand
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma