Administration of alpha-galactosylceramide impairs the survival of dendritic cell subpopulations in vivo

J Leukoc Biol. 2011 May;89(5):753-62. doi: 10.1189/jlb.0910480. Epub 2011 Feb 4.


In this study, we examine whether recognition of α-GalCer presented on CD1d-expressing DCs and B cells in vivo elicits the cytotoxic activity of iNKT cells and elimination of α-GalCer-presenting cells. We report that i.v. injection of α-GalCer induced a decrease in the percentage and number of splenic CD8(+)Langerin(+) DCs, while CD8(-) DCs were not affected. The decline in CD8(+) DC numbers was clearly detectable by 15 h after α-GalCer injection, was maximal at 24-48 h, returned to normal by day 7, and was accompanied by a reduced cross-presentation of OVA protein given i.v. to specific CD8(+) T cells in vitro. The decrease in the numbers of CD8(+) DCs required iNKT cells but was independent of perforin, Fas, or IFN-γ, as it was observed in mice deficient in each of these molecules. In contrast, treatment with a TNF-α-neutralizing antibody was effective at reducing the decline in CD8(+) DC numbers and DC activation. Treatment with immunostimulatory CpG ODN also resulted in DC activation and a decreased number of CD8(+) DCs; however, the decline in DC number was a result of down-regulation of CD11c and CD8 and did not require iNKT cells or TNF-α. Although CD8(+)Langerin(+) DCs appeared to be selectively affected by α-GalCer treatment, they were not required for early iNKT cell responses, as their prior depletion did not prevent the increase in serum TNF-α and IL-4 observed after α-GalCer treatment. Thus, iNKT cells regulate the survival of CD8(+) DCs through a mechanism that does not appear to involve direct cell killing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD1d / physiology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Survival / drug effects*
  • Cross-Priming / drug effects
  • Cross-Priming / immunology
  • Dendritic Cells / drug effects*
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Galactosylceramides / pharmacology*
  • Green Fluorescent Proteins / metabolism
  • Interferon-gamma / physiology
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Natural Killer T-Cells / drug effects*
  • Natural Killer T-Cells / metabolism
  • Spleen / cytology
  • Spleen / drug effects*
  • Spleen / metabolism
  • Tumor Necrosis Factor-alpha / physiology


  • Antigens, CD1d
  • Galactosylceramides
  • Tumor Necrosis Factor-alpha
  • alpha-galactosylceramide
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins
  • Interferon-gamma