Paradoxical effects of interleukin-10 on the maturation of murine myeloid dendritic cells

Immunology. 2003 Oct;110(2):188-96. doi: 10.1046/j.1365-2567.2003.01730.x.

Abstract

The immunoregulatory cytokine, interleukin-10 (IL-10), has been shown to inhibit the maturation of human myeloid dendritic cells (DC). In the present study, we demonstrate that IL-10 has paradoxical effects on the maturation of murine myeloid bone marrow-derived DC. On the one hand, IL-10 inhibits the maturation of murine myeloid DC. The addition of IL-10 to granulocyte-macrophage colony-stimulating factor (GM-CSF)-supported murine BM-derived DC cultures reduced the frequency of major histocompatibility complex (MHC) class IIbright cells. These IL-10-pretreated DC have a reduced capacity to stimulate T cells in an allogeneic mixed leucocyte reaction. On the other hand, however, and in contrast to the effects of IL-10 on human DC, we found that the addition of IL-10 from the initiation of the culture onwards induced an up-regulation of the expression of the costimulatory molecules CD40, CD80 and CD86 on murine myeloid DC, as compared to DC generated with GM-CSF only. Moreover, a subpopulation of IL-10-pretreated MHC class IIdim DC lacked the capacity to take up dextran-fluorescein isothiocyanate (FITC), a feature of DC maturation. Taken together, our data demonstrate that the generation of murine myeloid DC in the presence of IL-10 results in a population of incompletely matured MHC class IIdim CD80+ CD86+ DC. These DC lack T-cell stimulatory capacity, suggesting a role for IL-10 in conferring tolerogenic properties on murine myeloid DC.

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Differentiation / immunology
  • Cells, Cultured
  • Dendritic Cells / immunology*
  • Female
  • Genes, MHC Class II / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Immunophenotyping
  • Interleukin-10 / immunology*
  • Lipopolysaccharides / immunology
  • Lymphocyte Activation / immunology
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Myeloid Cells / immunology*
  • Up-Regulation / immunology

Substances

  • Lipopolysaccharides
  • Interleukin-10
  • Granulocyte-Macrophage Colony-Stimulating Factor