Polarization of Naive T Cells Into Th1 or Th2 by Distinct Cytokine-Driven Murine Dendritic Cell Populations: Implications for Immunotherapy

J Leukoc Biol. 2005 Sep;78(3):656-64. doi: 10.1189/jlb.1104631. Epub 2005 Jun 16.

Abstract

Dendritic cells (DCs) activate T cells and regulate their differentiation into T helper cell type 1 (Th1) and/or Th2 cells. To identify DCs with differing abilities to direct Th1/Th2 cell differentiation, we cultured mouse bone marrow progenitors in granulocyte macrophage-colony stimulating factor (GM), GM + interleukin (IL)-4, or GM + IL-15 and generated three distinct DC populations. The GM + IL-4 DCs expressed high levels of CD80/CD86 and major histocompatibility complex (MHC) class II and produced low levels of IL-12p70. GM and GM + IL-15 DCs expressed low levels of CD80/CD86 and MHC class II. The GM + IL-15 DCs produced high levels of IL-12p70 and interferon (IFN)-gamma, whereas GM DCs produced only high levels of IL-12p70. Naive T cells stimulated with GM + IL-4 DCs secreted high levels of IL-4 and IL-5 in addition to IFN-gamma. In contrast, the GM + IL-15 DCs induced higher IFN-gamma production by T cells with little or no Th2 cytokines. GM DCs did not induce T cell polarization, despite producing large amounts of IL-12p70 following activation. A similar pattern of T cell activation was observed after in vivo administration of DCs. These data suggest that IL-12p70 production alone, although necessary for Th1 differentiation, is not sufficient to induce Th1 responses. These studies have implications for the use of DC-based vaccines in immunotherapy of cancer and other clinical conditions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • B7-1 Antigen / biosynthesis
  • B7-1 Antigen / drug effects
  • B7-2 Antigen / biosynthesis
  • B7-2 Antigen / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / metabolism
  • Cell Differentiation / drug effects
  • Cell Differentiation / immunology
  • Cell Polarity / drug effects
  • Cell Polarity / immunology
  • Cell Polarity / physiology
  • Cells, Cultured
  • Dendritic Cells / cytology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Immunotherapy*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / drug effects
  • Interleukin-12 / biosynthesis
  • Interleukin-15 / biosynthesis
  • Interleukin-15 / immunology
  • Interleukin-15 / pharmacology
  • Interleukin-4 / biosynthesis
  • Interleukin-4 / immunology
  • Interleukin-4 / pharmacology
  • Mice
  • Mice, Inbred NOD
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Phenotype
  • Protein Subunits / biosynthesis
  • Protein Subunits / drug effects
  • Th1 Cells / drug effects
  • Th1 Cells / immunology*
  • Th2 Cells / drug effects
  • Th2 Cells / immunology*

Substances

  • B7-1 Antigen
  • B7-2 Antigen
  • Interleukin-15
  • Protein Subunits
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor