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Invariant NKT cells promote CD8(+) cytotoxic T cell responses by inducing CD70 expression on dendritic cells

Record type: Article

Activation of invariant NK T (iNKT) cells with the glycolipid alpha-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 alpha-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 alpha-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.

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Taraban, Vadim Y., Martin, Sonya, Attfield, Kathrine E., Glennie, Martin J., Elliott, Tim, Elewaut, Dirk, Van Calenbergh, Serge, Linclau, Bruno and Al-Shamkhani, Aymen (2008) Invariant NKT cells promote CD8(+) cytotoxic T cell responses by inducing CD70 expression on dendritic cells Journal of Immunology, 180, (7), pp. 4615-4620. (PMID:18354184).

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Published date: 2008
Keywords: monoclonal-antibody therapy, antigen, costimulation, lymph-nodes, alpha-galactosylceramide, adaptive immunity, cutting edge, cross-presentation, innate, nkt cells, in-vivo, mouse
Organisations: Faculty of Medicine, Chemistry, Cancer Sciences


Local EPrints ID: 62946
ISSN: 0022-1767
PURE UUID: 8a9317db-bd83-4a89-a4f1-ca5407eab0ca
ORCID for Tim Elliott: ORCID iD
ORCID for Bruno Linclau: ORCID iD

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Date deposited: 05 Sep 2008
Last modified: 17 Jul 2017 14:19

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Author: Vadim Y. Taraban
Author: Sonya Martin
Author: Kathrine E. Attfield
Author: Tim Elliott ORCID iD
Author: Dirk Elewaut
Author: Serge Van Calenbergh
Author: Bruno Linclau ORCID iD

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