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AbstractActivation of invariant NK T (iNKT) cells with the glycolipid α-galactosylceramide promotes CD8+ cytotoxic T cell responses, a property that has been used to enhance the efficacy of antitumor vaccines. Using chimeric mice, we now show that the adjuvant properties of iNKT cells require that CD40 triggering and Ag presentation to CD8+ T cells occur on the same APCs. We demonstrate that injection of α-galactosylceramide triggers CD70 expression on splenic T cell zone dendritic cells and that this is dependent on CD40 signaling. Importantly, we show that blocking the interaction between CD70 and CD27, its costimulatory receptor on T cells, abrogates the ability of iNKT cells to promote a CD8+ T cell response and abolishes the efficacy of α-GalCer as an adjuvant for antitumor vaccines. These results define a key role for CD70 in linking the innate response of iNKT cells to the activation of CD8+ T cells.

Original publication

DOI

10.4049/jimmunol.180.7.4615

Type

Journal article

Journal

The Journal of Immunology

Publisher

The American Association of Immunologists

Publication Date

01/04/2008

Volume

180

Pages

4615 - 4620