HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Taraban, V. Y. Articles by Al-Shamkhani, A. PubMed PubMed Citation Articles by Taraban, V. Y. Articles by Al-Shamkhani, A.

Invariant NKT Cells Promote CD8⁺ Cytotoxic T Cell Responses by Inducing CD70 Expression on Dendritic Cells¹

Vadim Y. Taraban^*, Sonya Martin^*, Kathrine E. Attfield^*, Martin J. Glennie^*, Tim Elliott^*, Dirk Elewaut, Serge Van Calenbergh, Bruno Linclau and Aymen Al-Shamkhani^2,*

^* Cancer Sciences Division, University of Southampton and School of Chemistry, University of Southampton, Southampton, United Kingdom; Department of Rheumatology, Laboratory of Molecular Immunology and Inflammation, Ghent University Hospital, Ghent, Belgium; and Laboratory of Medicinal Chemistry, Faculty of Pharmaceutical Sciences, Ghent University, Belgium

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

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was funded by grants from Cancer Research U.K., Tenovus, Wessex Medical Research, the Fund for Scientific Research Flanders, and the Research Council of Ghent University.

² Address correspondence and reprint requests to Dr. Aymen Al-Shamkhani, Tenovus Research Laboratory, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, U.K. E-mail address: aymen{at}soton.ac.uk

³ Abbreviations used in this paper: iNKT, invariant NKT cell; DC, dendritic cell; GalCer, -galactosylceramide; CD40L, CD40 ligand; OVAp, OVA peptide; WT, wild type; MR, mannose receptor.