Cross-presentation of glycolipid from tumor cells loaded with alpha-galactosylceramide leads to potent and long-lived T cell mediated immunity via dendritic cells.
We report a mechanism to induce combined and long-lived CD4(+) and CD8(+) T cell immunity to several mouse tumors. Surprisingly, the initial source of antigen is a single low dose of tumor cells loaded with alpha-galactosylceramide (alpha-GalCer) glycolipid (tumor/Gal) but lacking co-stimulatory molecules. After tumor/Gal injection intravenously (i.v.), innate NKT and NK cells reject the tumor cells, some of which are taken up by dendritic cells (DCs). The DCs in turn cross-present glycolipid on CD1d molecules to NKT cells and undergo maturation. For B16 melanoma cells loaded with alpha-GalCer (B16/Gal), interferon gamma-producing CD8(+) T cells develop toward several melanoma peptides, again after a single low i.v. dose of B16/Gal. In all four poorly immunogenic tumors tested, a single dose of tumor/Gal i.v. allows mice to become resistant to tumors given subcutaneously. Resistance requires CD4(+) and CD8(+) cells, as well as DCs, and persists for 6-12 mo. Therefore, several immunogenic features of DCs are engaged by the CD1d-mediated cross-presentation of glycolipid-loaded tumor cells, leading to particularly strong and long-lived adaptive immunity.
Shimizu
Kanako
K
Research Unit for Cellular Immunotherapy, Research Center for Allergy and Immunology, Institute of Physical and Chemical Research, Tsurumi-ku, Yokohama City, Kanagawa, 230-0045, Japan.
Kurosawa
Yuri
Y
Taniguchi
Masaru
M
Steinman
Ralph M
RM
Fujii
Shin-Ichiro
S
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D003713:Dendritic Cells / Q000276:immunology* / Q000637:transplantation; D005699:Galactosylceramides / Q000494:pharmacology*; D006017:Glycolipids / Q000302:isolation & purification / Q000494:pharmacology*; D007111:Immunity, Cellular; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology*
D019496:Cancer Vaccines; D005699:Galactosylceramides; D006017:Glycolipids; C493154:alpha-galactosylceramide