Prolonged IFN-gamma-producing NKT Response Induced With Alpha-Galactosylceramide-Loaded DCs

Nat Immunol. 2002 Sep;3(9):867-74. doi: 10.1038/ni827. Epub 2002 Aug 5.

Abstract

Natural killer T (NKT) lymphocytes mediate a rapid reaction to the glycolipid drug alpha-galactosylceramide (alpha GalCer), which triggers release of large amounts of cytokines into the serum within 12 h, starting with interleukin 4 (IL-4). When alpha GalCer is administered to mice on dendritic cells (DCs) instead, the response is more prolonged (>4 days) and marked by a large expansion in IFN-gamma-producing NKT cells as well as greater resistance to metastases of the B16 melanoma. Nevertheless, DCs from mice given free alpha GalCer are able to induce strong IFN-gamma-producing NKT responses when transferred to naïve mice, but not when transferred to alpha GalCer-treated recipients. In the latter, the NKT cells are energized and can respond to glycolipid only in the presence of supplemental IL-2. Therefore, when alpha GalCer is selectively targeted to DCs, mice develop a stronger, more prolonged and effector type of NKT response, but this response can be blocked by the induction of anergy after presentation of alpha GalCer on other cells.

MeSH terms

  • Animals
  • Dendritic Cells / physiology*
  • Female
  • Galactosylceramides / pharmacology*
  • Interferon-gamma / biosynthesis*
  • Interleukin-2 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Killer Cells, Natural / immunology*
  • Melanoma / prevention & control
  • Melanoma / secondary
  • Mice
  • Mice, Inbred C57BL

Substances

  • Galactosylceramides
  • Interleukin-2
  • Interleukin-4
  • Interferon-gamma