Cross-presentation of Glycolipid from Tumor Cells Loaded with Alpha-galactosylceramide Leads to Potent and Long-lived T Cell Mediated Immunity Via Dendritic Cells

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2007 Oct 10

PMID 17923500

Citations 78

Authors

Kanako Shimizu

Yuri Kurosawa

Masaru Taniguchi

Ralph M Steinman

Shin-Ichiro Fujii

Affiliations

Soon will be listed here.

Abstract

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.

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