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Institut National de la Santé et de la Recherche Médicale, Unité 547, Lille; Institut Pasteur de Lille, Lille; and Université de Lille 2, Lille, France
Unmethylated CpG oligodeoxynucleotides (ODNs), by activating cells of the innate immune system, such as dendritic cells and NK cells, are potent adjuvants for type 1 immune responses. In the present study, we aimed to investigate the role of invariant NKT (iNKT) cells, a subset of lipid-reactive innate lymphocytes, in CpG ODN-induced innate and acquired type 1 responses. Our data show that, in response to the CpG ODN type B 1826, splenic and hepatic iNKT cells become activated and produce IFN-
, but not IL-4, both in vitro and in vivo. This Th1 bias is independent from the Ag-presenting molecule CD1d and strongly requires IL-12, at least in vitro. We also report that iNKT cell activation, in response to CpG ODN type B, results in the transactivation of NK cells. To address the potential role of iNKT cells in type 1 innate immunity induced by CpG ODN, a murine model of malignant melanoma was used. We show that CpG ODN type B protects mice against B16F10-induced lung metastasis in wild-type mice, but in a less efficient manner in iNKT cell-deficient animals. Finally, we report that immunization of wild-type mice with CpG ODN type B plus keyhole limpet hemocyanin biases the immune response toward a Th1 direction, an effect strongly mediated by iNKT cells. We conclude that iNKT cells amplify the innate and acquired response to CpG ODN type B, with potentially important consequences for the regulation of immune responses.
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 supported by the Institut National de la Santé et de la Recherche Médicale, the Pasteur Institute of Lille, the University of Lille 2, and l’Agence Nationale de la Recherche (programme MIME). C.P., E.B., and T.M. were recipients of a doctoral fellowship from the Conseil Régional Nord Pas de Calais/Institut National de la Santé et de la Recherche Médicale (to C.P.) or from the Ministère de l’Education Nationale de la Recherche et Technique (to E.B. and T.M.). C.F. is supported by the Institut National de la Santé et de la Recherche Médicale and F.T. by the Centre National de la Recherche Scientifique.
2 Current address: Integrated Department of Immunology, University of Colorado Health Sciences Center, National Jewish Medical and Research Center, 1400 Jackson Street, Denver, CO 80206.
3 Address correspondence and reprint requests to Dr. François Trottein, Institut National de la Santé et de la Recherche Médicale, Unité 547, Institut Pasteur de Lille, 1, rue du Professeur Calmette, BP 245, 59019 Lille Cedex, France. E-mail address: francois.trottein{at}pasteur-lille.fr
4 Abbreviations used in this paper: ODN, oligonucleotide; DC, dendritic cell; iNKT, invariant NKT; 
-GalCer, -galactosylceramide; WT, wild type; MNC, mononuclear cell; KLH, keyhole limpet keyhole.
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