Prolonged IFN-gamma-producing NKT response induced with alpha-galactosylceramide-loaded DCs.
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.
Fujii
Shin-ichiro
S
Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA.
Shimizu
Kanako
K
Kronenberg
Mitchell
M
Steinman
Ralph M
RM
D000818:Animals; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D005699:Galactosylceramides / Q000494:pharmacology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000276:immunology*; D008545:Melanoma / Q000517:prevention & control / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL
D005699:Galactosylceramides; D007376:Interleukin-2; D015847:Interleukin-4; D007371:Interferon-gamma