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The Journal of Immunology, 2008, 181, 4452-4456
Copyright © 2008 by The American Association of Immunologists, Inc.

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Cutting Edge: The Mechanism of Invariant NKT Cell Responses to Viral Danger Signals1

Aaron J. Tyznik*, Emmanuel Tupin2,3,*, Niranjana A. Nagarajan2,4,*, Min J. Her{dagger}, Chris A. Benedict2,5,{dagger} and Mitchell Kronenberg2,5,*

* Division of Developmental Immunology and {dagger} Division of Molecular Immunology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037

Invariant NK T (iNKT) cells influence the response to viral infections, although the mechanisms are poorly defined. In this study we show that these innate-like lymphocytes secrete IFN-{gamma} upon culture with CpG oligodeoxynucleotide-stimulated dendritic cells (DCs) from mouse bone marrow. This requires TLR9 signaling and IL-12 secretion by the activated DCs, but it does not require CD1d expression. iNKT cells also produce IFN-{gamma} in response to mouse CMV infection. Their mechanism of mouse CMV detection is quite similar to that of CpG, requiring both TLR9 signaling and IL-12 secretion, while the need for CD1d expression is relatively minor. Consequently, iNKT cells have the ability to respond to a variety of microbes, including viruses, in an Ag-independent manner, suggesting they may play a broad role in antipathogen defenses despite their limited TCR repertoire.

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 National Institutes of Health Grants AI 69296, AI 71922 (to M.K.), and F32 AI 80087 (to A.J.T.).

2 E.T. and N.A.N. contributed equally to this manuscript; C. A. B. and M. K. share senior authorship.

3 Current address: Vironova AB, Smedjegatan 6, 131 34 Nacka, Sweden.

4 Current address: University of California Berkeley, Department of Molecular and Cell Biology, 425 Life Sciences, Addition no. 3200, Berkeley, CA 94720-3200.

5 Address correspondence and reprint requests to Dr. Chris Benedict or Dr. Mitchell Kronenberg, La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037. E-mail addresses: benedict{at}liai.org and mitch{at}liai.org

6 Abbreviations used in this paper: iNKT, invariant NK T (cell); DC, dendritic cell; {alpha}GalCer, {alpha}-galactosylceramide; hFlt3L, human fms-like tyrosine kinase-3 ligand; MCMV, mouse CMV; ODN, oligodeoxynucleotide; WT, wild type.




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